51
Kim Solez, MD

Transition transplant path to tissue engineer path new banff class 2017

Embed Size (px)

Citation preview

Kim Solez MD

Last year I described how nearly everyone went sightseeing to avoid regenerative medicine sessions at 2015 AST CEOT

This year CTRMS is a full partner with CST in upcoming Halifax meeting

The Pre-meeting for Banff 2019 in Pittsburgh will be devoted to Regenerative MedicineTissue Engineering Pathology No escape

A Year Makes Big Difference In 2017 Regenerative Medicine in Ascendancy

The Future and All That Jazz music and poetry initiative conveying important messages of science will be the main entertainment at the TERMIS-AM meeting in Charlotte NC with two hours of entertainment at the exhibit area on December 4th and three hours at the NASCAR Hall of Fame on December 5th

A Year Makes Big Difference In 2017 FAATJ is Main Entertainment for TERMIS

Aviv Regevrsquos Human Cell Atlas httpswwwhumancellatlasorg

characterization of all cells in human body by single cell analysis is both promoted and funded via social media (Chan Zuckerberg) If you are not on Facebook you know nothing about it and it will likely be bigger than the human genome project You will be caught napping Nothing about this at 2017 USCAP

In 2017 Human Cell Atlas Poised to Stealth Revolutionize Pathology and Regenerative Medicine via Facebook

Stem Cell Technologies on Google Trends ndash News Headlines and Forecast

Current transplant protocols reach fewer than 10 of those in need

Worldwide 12 million people are in need of transplantation for end stage organ failure Current transplant protocols reach fewer than 10 of this number Regenerative medicine can save the remaining 90 over one million people annually

Tissue engineered bladder

Regenerative Medicine Already Here Working for Tubular Organs Bladder Esophagus Vagina

ViaCyte Announces Highly Anticipated Encapsulation Clinical

Trial Site Expansion into Canada

JDRF-funded researcher Dr James Shapiro will be the lead investigator at the Canadian site TORONTO July 29 2015 -- ViaCyte Inc announced the opening of a second site in its Phase 12 trial for Type I Diabetes which utilizes PEC-01trade pancreatic progenitor cells and the proprietary Encaptrareg drug delivery system which is designed to protect the transplanted cells from a patientrsquos immune system

Regenerative Medicine Already Here Viacyte Trial for Diabetes Therapy

Double Think Stem Cells are Greatest Hope

and Greatest Hype Stem Cell Tourism

Estimated to be $3 Billion a Year Industry and

Growing with More than 700 Clinics Worldwide

Mason C et al Regen Med 2011 May6(3)265-72 doi 102217rme1128 Cell therapy industry billion dollar global business with unlimited potential

Timothy Caulfield - Stem Cell Tourism June 2015

httpswwwyoutubecomwatchv=B0r89nMtg10

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Regenerative Medicine Human Gene Editing Revisiting

Canadian Policy 2017

Science Confronting stem cell hype Professor Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Science Confronting stem cell hype Professor

Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

Stem cell hype Media portrayal of therapy translation MARCH 30 2015

Policy Options Athletes and unproven stem cell therapies JANUARY 01 2015

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continued

Research ethics and stem cells Is it time to re‐thinkcurrent approaches to oversight DECEMBER 04 2014

Representations of Stem Cell Clinics on Twitter DECEMBER 01 2014

Unproven stem cell-based interventions amp physicians professional obligations a qualitative study with medical regulatory authorities in Canada OCTOBER 14 2014 Professional Regulation A Potentially Valuable Tool in Responding to Stem Cell Tourism SEPTEMBER 09 2014

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continuedStem Cell Tourism and Public Education The Missing Elements SEPTEMBER 04 2014

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions FEBRUARY 03 2014 Commercialization and Stem Cell Research A Review of Emerging Issues

DECEMBER 20 2013 A Role for Patient Advocacy Groups in Countering the Premature Commercialization of Stem Cell Interventions

OCTOBER 01 2013

The Positive Aspects of Stem Cell Therapies

The True Hope Has Potential to Reverse Three

Looming Problems in Medicine

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

ldquoThey will never be able to reverse those

trendsrdquo Together we can do those things

reverse those trends make life good again

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

Nephrologists amp Renal Pathologists May Be Only People Still Employed in 2045

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Last year I described how nearly everyone went sightseeing to avoid regenerative medicine sessions at 2015 AST CEOT

This year CTRMS is a full partner with CST in upcoming Halifax meeting

The Pre-meeting for Banff 2019 in Pittsburgh will be devoted to Regenerative MedicineTissue Engineering Pathology No escape

A Year Makes Big Difference In 2017 Regenerative Medicine in Ascendancy

The Future and All That Jazz music and poetry initiative conveying important messages of science will be the main entertainment at the TERMIS-AM meeting in Charlotte NC with two hours of entertainment at the exhibit area on December 4th and three hours at the NASCAR Hall of Fame on December 5th

A Year Makes Big Difference In 2017 FAATJ is Main Entertainment for TERMIS

Aviv Regevrsquos Human Cell Atlas httpswwwhumancellatlasorg

characterization of all cells in human body by single cell analysis is both promoted and funded via social media (Chan Zuckerberg) If you are not on Facebook you know nothing about it and it will likely be bigger than the human genome project You will be caught napping Nothing about this at 2017 USCAP

In 2017 Human Cell Atlas Poised to Stealth Revolutionize Pathology and Regenerative Medicine via Facebook

Stem Cell Technologies on Google Trends ndash News Headlines and Forecast

Current transplant protocols reach fewer than 10 of those in need

Worldwide 12 million people are in need of transplantation for end stage organ failure Current transplant protocols reach fewer than 10 of this number Regenerative medicine can save the remaining 90 over one million people annually

Tissue engineered bladder

Regenerative Medicine Already Here Working for Tubular Organs Bladder Esophagus Vagina

ViaCyte Announces Highly Anticipated Encapsulation Clinical

Trial Site Expansion into Canada

JDRF-funded researcher Dr James Shapiro will be the lead investigator at the Canadian site TORONTO July 29 2015 -- ViaCyte Inc announced the opening of a second site in its Phase 12 trial for Type I Diabetes which utilizes PEC-01trade pancreatic progenitor cells and the proprietary Encaptrareg drug delivery system which is designed to protect the transplanted cells from a patientrsquos immune system

Regenerative Medicine Already Here Viacyte Trial for Diabetes Therapy

Double Think Stem Cells are Greatest Hope

and Greatest Hype Stem Cell Tourism

Estimated to be $3 Billion a Year Industry and

Growing with More than 700 Clinics Worldwide

Mason C et al Regen Med 2011 May6(3)265-72 doi 102217rme1128 Cell therapy industry billion dollar global business with unlimited potential

Timothy Caulfield - Stem Cell Tourism June 2015

httpswwwyoutubecomwatchv=B0r89nMtg10

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Regenerative Medicine Human Gene Editing Revisiting

Canadian Policy 2017

Science Confronting stem cell hype Professor Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Science Confronting stem cell hype Professor

Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

Stem cell hype Media portrayal of therapy translation MARCH 30 2015

Policy Options Athletes and unproven stem cell therapies JANUARY 01 2015

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continued

Research ethics and stem cells Is it time to re‐thinkcurrent approaches to oversight DECEMBER 04 2014

Representations of Stem Cell Clinics on Twitter DECEMBER 01 2014

Unproven stem cell-based interventions amp physicians professional obligations a qualitative study with medical regulatory authorities in Canada OCTOBER 14 2014 Professional Regulation A Potentially Valuable Tool in Responding to Stem Cell Tourism SEPTEMBER 09 2014

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continuedStem Cell Tourism and Public Education The Missing Elements SEPTEMBER 04 2014

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions FEBRUARY 03 2014 Commercialization and Stem Cell Research A Review of Emerging Issues

DECEMBER 20 2013 A Role for Patient Advocacy Groups in Countering the Premature Commercialization of Stem Cell Interventions

OCTOBER 01 2013

The Positive Aspects of Stem Cell Therapies

The True Hope Has Potential to Reverse Three

Looming Problems in Medicine

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

ldquoThey will never be able to reverse those

trendsrdquo Together we can do those things

reverse those trends make life good again

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

Nephrologists amp Renal Pathologists May Be Only People Still Employed in 2045

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

The Future and All That Jazz music and poetry initiative conveying important messages of science will be the main entertainment at the TERMIS-AM meeting in Charlotte NC with two hours of entertainment at the exhibit area on December 4th and three hours at the NASCAR Hall of Fame on December 5th

A Year Makes Big Difference In 2017 FAATJ is Main Entertainment for TERMIS

Aviv Regevrsquos Human Cell Atlas httpswwwhumancellatlasorg

characterization of all cells in human body by single cell analysis is both promoted and funded via social media (Chan Zuckerberg) If you are not on Facebook you know nothing about it and it will likely be bigger than the human genome project You will be caught napping Nothing about this at 2017 USCAP

In 2017 Human Cell Atlas Poised to Stealth Revolutionize Pathology and Regenerative Medicine via Facebook

Stem Cell Technologies on Google Trends ndash News Headlines and Forecast

Current transplant protocols reach fewer than 10 of those in need

Worldwide 12 million people are in need of transplantation for end stage organ failure Current transplant protocols reach fewer than 10 of this number Regenerative medicine can save the remaining 90 over one million people annually

Tissue engineered bladder

Regenerative Medicine Already Here Working for Tubular Organs Bladder Esophagus Vagina

ViaCyte Announces Highly Anticipated Encapsulation Clinical

Trial Site Expansion into Canada

JDRF-funded researcher Dr James Shapiro will be the lead investigator at the Canadian site TORONTO July 29 2015 -- ViaCyte Inc announced the opening of a second site in its Phase 12 trial for Type I Diabetes which utilizes PEC-01trade pancreatic progenitor cells and the proprietary Encaptrareg drug delivery system which is designed to protect the transplanted cells from a patientrsquos immune system

Regenerative Medicine Already Here Viacyte Trial for Diabetes Therapy

Double Think Stem Cells are Greatest Hope

and Greatest Hype Stem Cell Tourism

Estimated to be $3 Billion a Year Industry and

Growing with More than 700 Clinics Worldwide

Mason C et al Regen Med 2011 May6(3)265-72 doi 102217rme1128 Cell therapy industry billion dollar global business with unlimited potential

Timothy Caulfield - Stem Cell Tourism June 2015

httpswwwyoutubecomwatchv=B0r89nMtg10

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Regenerative Medicine Human Gene Editing Revisiting

Canadian Policy 2017

Science Confronting stem cell hype Professor Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Science Confronting stem cell hype Professor

Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

Stem cell hype Media portrayal of therapy translation MARCH 30 2015

Policy Options Athletes and unproven stem cell therapies JANUARY 01 2015

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continued

Research ethics and stem cells Is it time to re‐thinkcurrent approaches to oversight DECEMBER 04 2014

Representations of Stem Cell Clinics on Twitter DECEMBER 01 2014

Unproven stem cell-based interventions amp physicians professional obligations a qualitative study with medical regulatory authorities in Canada OCTOBER 14 2014 Professional Regulation A Potentially Valuable Tool in Responding to Stem Cell Tourism SEPTEMBER 09 2014

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continuedStem Cell Tourism and Public Education The Missing Elements SEPTEMBER 04 2014

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions FEBRUARY 03 2014 Commercialization and Stem Cell Research A Review of Emerging Issues

DECEMBER 20 2013 A Role for Patient Advocacy Groups in Countering the Premature Commercialization of Stem Cell Interventions

OCTOBER 01 2013

The Positive Aspects of Stem Cell Therapies

The True Hope Has Potential to Reverse Three

Looming Problems in Medicine

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

ldquoThey will never be able to reverse those

trendsrdquo Together we can do those things

reverse those trends make life good again

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

Nephrologists amp Renal Pathologists May Be Only People Still Employed in 2045

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Aviv Regevrsquos Human Cell Atlas httpswwwhumancellatlasorg

characterization of all cells in human body by single cell analysis is both promoted and funded via social media (Chan Zuckerberg) If you are not on Facebook you know nothing about it and it will likely be bigger than the human genome project You will be caught napping Nothing about this at 2017 USCAP

In 2017 Human Cell Atlas Poised to Stealth Revolutionize Pathology and Regenerative Medicine via Facebook

Stem Cell Technologies on Google Trends ndash News Headlines and Forecast

Current transplant protocols reach fewer than 10 of those in need

Worldwide 12 million people are in need of transplantation for end stage organ failure Current transplant protocols reach fewer than 10 of this number Regenerative medicine can save the remaining 90 over one million people annually

Tissue engineered bladder

Regenerative Medicine Already Here Working for Tubular Organs Bladder Esophagus Vagina

ViaCyte Announces Highly Anticipated Encapsulation Clinical

Trial Site Expansion into Canada

JDRF-funded researcher Dr James Shapiro will be the lead investigator at the Canadian site TORONTO July 29 2015 -- ViaCyte Inc announced the opening of a second site in its Phase 12 trial for Type I Diabetes which utilizes PEC-01trade pancreatic progenitor cells and the proprietary Encaptrareg drug delivery system which is designed to protect the transplanted cells from a patientrsquos immune system

Regenerative Medicine Already Here Viacyte Trial for Diabetes Therapy

Double Think Stem Cells are Greatest Hope

and Greatest Hype Stem Cell Tourism

Estimated to be $3 Billion a Year Industry and

Growing with More than 700 Clinics Worldwide

Mason C et al Regen Med 2011 May6(3)265-72 doi 102217rme1128 Cell therapy industry billion dollar global business with unlimited potential

Timothy Caulfield - Stem Cell Tourism June 2015

httpswwwyoutubecomwatchv=B0r89nMtg10

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Regenerative Medicine Human Gene Editing Revisiting

Canadian Policy 2017

Science Confronting stem cell hype Professor Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Science Confronting stem cell hype Professor

Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

Stem cell hype Media portrayal of therapy translation MARCH 30 2015

Policy Options Athletes and unproven stem cell therapies JANUARY 01 2015

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continued

Research ethics and stem cells Is it time to re‐thinkcurrent approaches to oversight DECEMBER 04 2014

Representations of Stem Cell Clinics on Twitter DECEMBER 01 2014

Unproven stem cell-based interventions amp physicians professional obligations a qualitative study with medical regulatory authorities in Canada OCTOBER 14 2014 Professional Regulation A Potentially Valuable Tool in Responding to Stem Cell Tourism SEPTEMBER 09 2014

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continuedStem Cell Tourism and Public Education The Missing Elements SEPTEMBER 04 2014

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions FEBRUARY 03 2014 Commercialization and Stem Cell Research A Review of Emerging Issues

DECEMBER 20 2013 A Role for Patient Advocacy Groups in Countering the Premature Commercialization of Stem Cell Interventions

OCTOBER 01 2013

The Positive Aspects of Stem Cell Therapies

The True Hope Has Potential to Reverse Three

Looming Problems in Medicine

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

ldquoThey will never be able to reverse those

trendsrdquo Together we can do those things

reverse those trends make life good again

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

Nephrologists amp Renal Pathologists May Be Only People Still Employed in 2045

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Stem Cell Technologies on Google Trends ndash News Headlines and Forecast

Current transplant protocols reach fewer than 10 of those in need

Worldwide 12 million people are in need of transplantation for end stage organ failure Current transplant protocols reach fewer than 10 of this number Regenerative medicine can save the remaining 90 over one million people annually

Tissue engineered bladder

Regenerative Medicine Already Here Working for Tubular Organs Bladder Esophagus Vagina

ViaCyte Announces Highly Anticipated Encapsulation Clinical

Trial Site Expansion into Canada

JDRF-funded researcher Dr James Shapiro will be the lead investigator at the Canadian site TORONTO July 29 2015 -- ViaCyte Inc announced the opening of a second site in its Phase 12 trial for Type I Diabetes which utilizes PEC-01trade pancreatic progenitor cells and the proprietary Encaptrareg drug delivery system which is designed to protect the transplanted cells from a patientrsquos immune system

Regenerative Medicine Already Here Viacyte Trial for Diabetes Therapy

Double Think Stem Cells are Greatest Hope

and Greatest Hype Stem Cell Tourism

Estimated to be $3 Billion a Year Industry and

Growing with More than 700 Clinics Worldwide

Mason C et al Regen Med 2011 May6(3)265-72 doi 102217rme1128 Cell therapy industry billion dollar global business with unlimited potential

Timothy Caulfield - Stem Cell Tourism June 2015

httpswwwyoutubecomwatchv=B0r89nMtg10

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Regenerative Medicine Human Gene Editing Revisiting

Canadian Policy 2017

Science Confronting stem cell hype Professor Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Science Confronting stem cell hype Professor

Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

Stem cell hype Media portrayal of therapy translation MARCH 30 2015

Policy Options Athletes and unproven stem cell therapies JANUARY 01 2015

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continued

Research ethics and stem cells Is it time to re‐thinkcurrent approaches to oversight DECEMBER 04 2014

Representations of Stem Cell Clinics on Twitter DECEMBER 01 2014

Unproven stem cell-based interventions amp physicians professional obligations a qualitative study with medical regulatory authorities in Canada OCTOBER 14 2014 Professional Regulation A Potentially Valuable Tool in Responding to Stem Cell Tourism SEPTEMBER 09 2014

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continuedStem Cell Tourism and Public Education The Missing Elements SEPTEMBER 04 2014

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions FEBRUARY 03 2014 Commercialization and Stem Cell Research A Review of Emerging Issues

DECEMBER 20 2013 A Role for Patient Advocacy Groups in Countering the Premature Commercialization of Stem Cell Interventions

OCTOBER 01 2013

The Positive Aspects of Stem Cell Therapies

The True Hope Has Potential to Reverse Three

Looming Problems in Medicine

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

ldquoThey will never be able to reverse those

trendsrdquo Together we can do those things

reverse those trends make life good again

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

Nephrologists amp Renal Pathologists May Be Only People Still Employed in 2045

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Current transplant protocols reach fewer than 10 of those in need

Worldwide 12 million people are in need of transplantation for end stage organ failure Current transplant protocols reach fewer than 10 of this number Regenerative medicine can save the remaining 90 over one million people annually

Tissue engineered bladder

Regenerative Medicine Already Here Working for Tubular Organs Bladder Esophagus Vagina

ViaCyte Announces Highly Anticipated Encapsulation Clinical

Trial Site Expansion into Canada

JDRF-funded researcher Dr James Shapiro will be the lead investigator at the Canadian site TORONTO July 29 2015 -- ViaCyte Inc announced the opening of a second site in its Phase 12 trial for Type I Diabetes which utilizes PEC-01trade pancreatic progenitor cells and the proprietary Encaptrareg drug delivery system which is designed to protect the transplanted cells from a patientrsquos immune system

Regenerative Medicine Already Here Viacyte Trial for Diabetes Therapy

Double Think Stem Cells are Greatest Hope

and Greatest Hype Stem Cell Tourism

Estimated to be $3 Billion a Year Industry and

Growing with More than 700 Clinics Worldwide

Mason C et al Regen Med 2011 May6(3)265-72 doi 102217rme1128 Cell therapy industry billion dollar global business with unlimited potential

Timothy Caulfield - Stem Cell Tourism June 2015

httpswwwyoutubecomwatchv=B0r89nMtg10

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Regenerative Medicine Human Gene Editing Revisiting

Canadian Policy 2017

Science Confronting stem cell hype Professor Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Science Confronting stem cell hype Professor

Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

Stem cell hype Media portrayal of therapy translation MARCH 30 2015

Policy Options Athletes and unproven stem cell therapies JANUARY 01 2015

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continued

Research ethics and stem cells Is it time to re‐thinkcurrent approaches to oversight DECEMBER 04 2014

Representations of Stem Cell Clinics on Twitter DECEMBER 01 2014

Unproven stem cell-based interventions amp physicians professional obligations a qualitative study with medical regulatory authorities in Canada OCTOBER 14 2014 Professional Regulation A Potentially Valuable Tool in Responding to Stem Cell Tourism SEPTEMBER 09 2014

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continuedStem Cell Tourism and Public Education The Missing Elements SEPTEMBER 04 2014

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions FEBRUARY 03 2014 Commercialization and Stem Cell Research A Review of Emerging Issues

DECEMBER 20 2013 A Role for Patient Advocacy Groups in Countering the Premature Commercialization of Stem Cell Interventions

OCTOBER 01 2013

The Positive Aspects of Stem Cell Therapies

The True Hope Has Potential to Reverse Three

Looming Problems in Medicine

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

ldquoThey will never be able to reverse those

trendsrdquo Together we can do those things

reverse those trends make life good again

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

Nephrologists amp Renal Pathologists May Be Only People Still Employed in 2045

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Worldwide 12 million people are in need of transplantation for end stage organ failure Current transplant protocols reach fewer than 10 of this number Regenerative medicine can save the remaining 90 over one million people annually

Tissue engineered bladder

Regenerative Medicine Already Here Working for Tubular Organs Bladder Esophagus Vagina

ViaCyte Announces Highly Anticipated Encapsulation Clinical

Trial Site Expansion into Canada

JDRF-funded researcher Dr James Shapiro will be the lead investigator at the Canadian site TORONTO July 29 2015 -- ViaCyte Inc announced the opening of a second site in its Phase 12 trial for Type I Diabetes which utilizes PEC-01trade pancreatic progenitor cells and the proprietary Encaptrareg drug delivery system which is designed to protect the transplanted cells from a patientrsquos immune system

Regenerative Medicine Already Here Viacyte Trial for Diabetes Therapy

Double Think Stem Cells are Greatest Hope

and Greatest Hype Stem Cell Tourism

Estimated to be $3 Billion a Year Industry and

Growing with More than 700 Clinics Worldwide

Mason C et al Regen Med 2011 May6(3)265-72 doi 102217rme1128 Cell therapy industry billion dollar global business with unlimited potential

Timothy Caulfield - Stem Cell Tourism June 2015

httpswwwyoutubecomwatchv=B0r89nMtg10

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Regenerative Medicine Human Gene Editing Revisiting

Canadian Policy 2017

Science Confronting stem cell hype Professor Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Science Confronting stem cell hype Professor

Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

Stem cell hype Media portrayal of therapy translation MARCH 30 2015

Policy Options Athletes and unproven stem cell therapies JANUARY 01 2015

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continued

Research ethics and stem cells Is it time to re‐thinkcurrent approaches to oversight DECEMBER 04 2014

Representations of Stem Cell Clinics on Twitter DECEMBER 01 2014

Unproven stem cell-based interventions amp physicians professional obligations a qualitative study with medical regulatory authorities in Canada OCTOBER 14 2014 Professional Regulation A Potentially Valuable Tool in Responding to Stem Cell Tourism SEPTEMBER 09 2014

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continuedStem Cell Tourism and Public Education The Missing Elements SEPTEMBER 04 2014

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions FEBRUARY 03 2014 Commercialization and Stem Cell Research A Review of Emerging Issues

DECEMBER 20 2013 A Role for Patient Advocacy Groups in Countering the Premature Commercialization of Stem Cell Interventions

OCTOBER 01 2013

The Positive Aspects of Stem Cell Therapies

The True Hope Has Potential to Reverse Three

Looming Problems in Medicine

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

ldquoThey will never be able to reverse those

trendsrdquo Together we can do those things

reverse those trends make life good again

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

Nephrologists amp Renal Pathologists May Be Only People Still Employed in 2045

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Tissue engineered bladder

Regenerative Medicine Already Here Working for Tubular Organs Bladder Esophagus Vagina

ViaCyte Announces Highly Anticipated Encapsulation Clinical

Trial Site Expansion into Canada

JDRF-funded researcher Dr James Shapiro will be the lead investigator at the Canadian site TORONTO July 29 2015 -- ViaCyte Inc announced the opening of a second site in its Phase 12 trial for Type I Diabetes which utilizes PEC-01trade pancreatic progenitor cells and the proprietary Encaptrareg drug delivery system which is designed to protect the transplanted cells from a patientrsquos immune system

Regenerative Medicine Already Here Viacyte Trial for Diabetes Therapy

Double Think Stem Cells are Greatest Hope

and Greatest Hype Stem Cell Tourism

Estimated to be $3 Billion a Year Industry and

Growing with More than 700 Clinics Worldwide

Mason C et al Regen Med 2011 May6(3)265-72 doi 102217rme1128 Cell therapy industry billion dollar global business with unlimited potential

Timothy Caulfield - Stem Cell Tourism June 2015

httpswwwyoutubecomwatchv=B0r89nMtg10

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Regenerative Medicine Human Gene Editing Revisiting

Canadian Policy 2017

Science Confronting stem cell hype Professor Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Science Confronting stem cell hype Professor

Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

Stem cell hype Media portrayal of therapy translation MARCH 30 2015

Policy Options Athletes and unproven stem cell therapies JANUARY 01 2015

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continued

Research ethics and stem cells Is it time to re‐thinkcurrent approaches to oversight DECEMBER 04 2014

Representations of Stem Cell Clinics on Twitter DECEMBER 01 2014

Unproven stem cell-based interventions amp physicians professional obligations a qualitative study with medical regulatory authorities in Canada OCTOBER 14 2014 Professional Regulation A Potentially Valuable Tool in Responding to Stem Cell Tourism SEPTEMBER 09 2014

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continuedStem Cell Tourism and Public Education The Missing Elements SEPTEMBER 04 2014

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions FEBRUARY 03 2014 Commercialization and Stem Cell Research A Review of Emerging Issues

DECEMBER 20 2013 A Role for Patient Advocacy Groups in Countering the Premature Commercialization of Stem Cell Interventions

OCTOBER 01 2013

The Positive Aspects of Stem Cell Therapies

The True Hope Has Potential to Reverse Three

Looming Problems in Medicine

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

ldquoThey will never be able to reverse those

trendsrdquo Together we can do those things

reverse those trends make life good again

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

Nephrologists amp Renal Pathologists May Be Only People Still Employed in 2045

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

ViaCyte Announces Highly Anticipated Encapsulation Clinical

Trial Site Expansion into Canada

JDRF-funded researcher Dr James Shapiro will be the lead investigator at the Canadian site TORONTO July 29 2015 -- ViaCyte Inc announced the opening of a second site in its Phase 12 trial for Type I Diabetes which utilizes PEC-01trade pancreatic progenitor cells and the proprietary Encaptrareg drug delivery system which is designed to protect the transplanted cells from a patientrsquos immune system

Regenerative Medicine Already Here Viacyte Trial for Diabetes Therapy

Double Think Stem Cells are Greatest Hope

and Greatest Hype Stem Cell Tourism

Estimated to be $3 Billion a Year Industry and

Growing with More than 700 Clinics Worldwide

Mason C et al Regen Med 2011 May6(3)265-72 doi 102217rme1128 Cell therapy industry billion dollar global business with unlimited potential

Timothy Caulfield - Stem Cell Tourism June 2015

httpswwwyoutubecomwatchv=B0r89nMtg10

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Regenerative Medicine Human Gene Editing Revisiting

Canadian Policy 2017

Science Confronting stem cell hype Professor Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Science Confronting stem cell hype Professor

Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

Stem cell hype Media portrayal of therapy translation MARCH 30 2015

Policy Options Athletes and unproven stem cell therapies JANUARY 01 2015

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continued

Research ethics and stem cells Is it time to re‐thinkcurrent approaches to oversight DECEMBER 04 2014

Representations of Stem Cell Clinics on Twitter DECEMBER 01 2014

Unproven stem cell-based interventions amp physicians professional obligations a qualitative study with medical regulatory authorities in Canada OCTOBER 14 2014 Professional Regulation A Potentially Valuable Tool in Responding to Stem Cell Tourism SEPTEMBER 09 2014

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continuedStem Cell Tourism and Public Education The Missing Elements SEPTEMBER 04 2014

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions FEBRUARY 03 2014 Commercialization and Stem Cell Research A Review of Emerging Issues

DECEMBER 20 2013 A Role for Patient Advocacy Groups in Countering the Premature Commercialization of Stem Cell Interventions

OCTOBER 01 2013

The Positive Aspects of Stem Cell Therapies

The True Hope Has Potential to Reverse Three

Looming Problems in Medicine

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

ldquoThey will never be able to reverse those

trendsrdquo Together we can do those things

reverse those trends make life good again

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

Nephrologists amp Renal Pathologists May Be Only People Still Employed in 2045

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Double Think Stem Cells are Greatest Hope

and Greatest Hype Stem Cell Tourism

Estimated to be $3 Billion a Year Industry and

Growing with More than 700 Clinics Worldwide

Mason C et al Regen Med 2011 May6(3)265-72 doi 102217rme1128 Cell therapy industry billion dollar global business with unlimited potential

Timothy Caulfield - Stem Cell Tourism June 2015

httpswwwyoutubecomwatchv=B0r89nMtg10

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Regenerative Medicine Human Gene Editing Revisiting

Canadian Policy 2017

Science Confronting stem cell hype Professor Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Science Confronting stem cell hype Professor

Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

Stem cell hype Media portrayal of therapy translation MARCH 30 2015

Policy Options Athletes and unproven stem cell therapies JANUARY 01 2015

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continued

Research ethics and stem cells Is it time to re‐thinkcurrent approaches to oversight DECEMBER 04 2014

Representations of Stem Cell Clinics on Twitter DECEMBER 01 2014

Unproven stem cell-based interventions amp physicians professional obligations a qualitative study with medical regulatory authorities in Canada OCTOBER 14 2014 Professional Regulation A Potentially Valuable Tool in Responding to Stem Cell Tourism SEPTEMBER 09 2014

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continuedStem Cell Tourism and Public Education The Missing Elements SEPTEMBER 04 2014

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions FEBRUARY 03 2014 Commercialization and Stem Cell Research A Review of Emerging Issues

DECEMBER 20 2013 A Role for Patient Advocacy Groups in Countering the Premature Commercialization of Stem Cell Interventions

OCTOBER 01 2013

The Positive Aspects of Stem Cell Therapies

The True Hope Has Potential to Reverse Three

Looming Problems in Medicine

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

ldquoThey will never be able to reverse those

trendsrdquo Together we can do those things

reverse those trends make life good again

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

Nephrologists amp Renal Pathologists May Be Only People Still Employed in 2045

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Regenerative Medicine Human Gene Editing Revisiting

Canadian Policy 2017

Science Confronting stem cell hype Professor Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Science Confronting stem cell hype Professor

Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

Stem cell hype Media portrayal of therapy translation MARCH 30 2015

Policy Options Athletes and unproven stem cell therapies JANUARY 01 2015

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continued

Research ethics and stem cells Is it time to re‐thinkcurrent approaches to oversight DECEMBER 04 2014

Representations of Stem Cell Clinics on Twitter DECEMBER 01 2014

Unproven stem cell-based interventions amp physicians professional obligations a qualitative study with medical regulatory authorities in Canada OCTOBER 14 2014 Professional Regulation A Potentially Valuable Tool in Responding to Stem Cell Tourism SEPTEMBER 09 2014

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continuedStem Cell Tourism and Public Education The Missing Elements SEPTEMBER 04 2014

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions FEBRUARY 03 2014 Commercialization and Stem Cell Research A Review of Emerging Issues

DECEMBER 20 2013 A Role for Patient Advocacy Groups in Countering the Premature Commercialization of Stem Cell Interventions

OCTOBER 01 2013

The Positive Aspects of Stem Cell Therapies

The True Hope Has Potential to Reverse Three

Looming Problems in Medicine

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

ldquoThey will never be able to reverse those

trendsrdquo Together we can do those things

reverse those trends make life good again

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

Nephrologists amp Renal Pathologists May Be Only People Still Employed in 2045

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsas

px Stem cell Publications Science Confronting stem cell hype Professor

Timothy Caulfield co-authors new stem cell policy guidelines MAY 13 2016

Stem cell hype Media portrayal of therapy translation MARCH 30 2015

Policy Options Athletes and unproven stem cell therapies JANUARY 01 2015

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continued

Research ethics and stem cells Is it time to re‐thinkcurrent approaches to oversight DECEMBER 04 2014

Representations of Stem Cell Clinics on Twitter DECEMBER 01 2014

Unproven stem cell-based interventions amp physicians professional obligations a qualitative study with medical regulatory authorities in Canada OCTOBER 14 2014 Professional Regulation A Potentially Valuable Tool in Responding to Stem Cell Tourism SEPTEMBER 09 2014

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continuedStem Cell Tourism and Public Education The Missing Elements SEPTEMBER 04 2014

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions FEBRUARY 03 2014 Commercialization and Stem Cell Research A Review of Emerging Issues

DECEMBER 20 2013 A Role for Patient Advocacy Groups in Countering the Premature Commercialization of Stem Cell Interventions

OCTOBER 01 2013

The Positive Aspects of Stem Cell Therapies

The True Hope Has Potential to Reverse Three

Looming Problems in Medicine

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

ldquoThey will never be able to reverse those

trendsrdquo Together we can do those things

reverse those trends make life good again

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

Nephrologists amp Renal Pathologists May Be Only People Still Employed in 2045

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continued

Research ethics and stem cells Is it time to re‐thinkcurrent approaches to oversight DECEMBER 04 2014

Representations of Stem Cell Clinics on Twitter DECEMBER 01 2014

Unproven stem cell-based interventions amp physicians professional obligations a qualitative study with medical regulatory authorities in Canada OCTOBER 14 2014 Professional Regulation A Potentially Valuable Tool in Responding to Stem Cell Tourism SEPTEMBER 09 2014

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continuedStem Cell Tourism and Public Education The Missing Elements SEPTEMBER 04 2014

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions FEBRUARY 03 2014 Commercialization and Stem Cell Research A Review of Emerging Issues

DECEMBER 20 2013 A Role for Patient Advocacy Groups in Countering the Premature Commercialization of Stem Cell Interventions

OCTOBER 01 2013

The Positive Aspects of Stem Cell Therapies

The True Hope Has Potential to Reverse Three

Looming Problems in Medicine

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

ldquoThey will never be able to reverse those

trendsrdquo Together we can do those things

reverse those trends make life good again

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

Nephrologists amp Renal Pathologists May Be Only People Still Employed in 2045

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

University of Alberta Health Law Institute

httpwwwhliualbertacaenPublicationsaspx

Stem cell publications continuedStem Cell Tourism and Public Education The Missing Elements SEPTEMBER 04 2014

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions FEBRUARY 03 2014 Commercialization and Stem Cell Research A Review of Emerging Issues

DECEMBER 20 2013 A Role for Patient Advocacy Groups in Countering the Premature Commercialization of Stem Cell Interventions

OCTOBER 01 2013

The Positive Aspects of Stem Cell Therapies

The True Hope Has Potential to Reverse Three

Looming Problems in Medicine

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

ldquoThey will never be able to reverse those

trendsrdquo Together we can do those things

reverse those trends make life good again

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

Nephrologists amp Renal Pathologists May Be Only People Still Employed in 2045

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

The Positive Aspects of Stem Cell Therapies

The True Hope Has Potential to Reverse Three

Looming Problems in Medicine

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

ldquoThey will never be able to reverse those

trendsrdquo Together we can do those things

reverse those trends make life good again

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

Nephrologists amp Renal Pathologists May Be Only People Still Employed in 2045

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

ldquoThey will never be able to reverse those

trendsrdquo Together we can do those things

reverse those trends make life good again

1 The loss of ldquolusterrdquo in transplantation

2 Workforce problems in nephrology due to lack of appeal to young peoplepotential trainees worldwide

3 Technological unemployment in medicine due to

Nephrologists amp Renal Pathologists May Be Only People Still Employed in 2045

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Nephrologists amp Renal Pathologists May Be Only People Still Employed in 2045

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney began

1991 updated and expanded every two years in

consensus meeting

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Banff Lesion Scoring Sign of Educated Tx Pathologist

imprimatur 1 The formula (=lsquolet it be printedrsquo) signed by an official authorizing printing of a bookhence as sb an official license to print

The Oxford English Dictionary (2nd ed)

Banff lesion scoring g cg i ci t ct v cv ah mm ptc C4d

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

1991 First Conference

1993 First Kidney International publication

1995 Integration with CADI

1997 Integration with CCTT classification

1999 Second KI paper Clinical practice guidelines Implantation biopsies

2001 Classification of antibody-mediated rejection Regulatory agencies participating

2003 Genomics focus ptc cell accumulation scoring

2005 Gene chip analysis Elimination of CAN identification of chronic antibody-mediated rejection

2007 First meeting far from a town called ldquoBanffrdquo ndash La Coruna Spain

2009 Working groups Meeting in Banff Alberta Canada

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Significance of lsquoBanff papersrsquo

bull More than 5000 citations of the 14 Banff meeting reports

bull 977 Banff Transplantation papers in PubMed

bull Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

bull 3 Banff meeting reports are among the top 4 cited AJT articles

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Tissue Engineering Pathology Added Soon

bull

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g i t v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

ldquoOmicsrdquo-specialists

Off-springsLiver

Pancreas

Lung Heart

CTA

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees K Solez (Chair) L Racusen D Glotz J Demetris M Mengel M Mihatsch D Seron

2015 Local Conference chair Michael Mengel

Organ Steering committee ChairsComposite tissues Linda CendalesHeart Patrick BrunevalKidney Mark HaasLiver Jake DemetrisLung William Wallace and Carol FarverPancreas Cinthia Drachenberg

Banff Working Group (BWG) LeadsMolecular transplantation pathology Michael Mengel Banu SisIsolated v-lesions Banu Sis Ed KrausQuality assurance in transplantation diagnostics Michael Mengel and Parmjeet RandhawaC4d-negative ABMR Mark Haas Banu Sis Alexandre LoupyFibrosis scoring Robert Colvin Brad Farris Michael MengelDigital Pathology in Transplantation Jake Demetris

2015 Scientific program committeeAlex Loupy (Chair)Mark Haas Banu Sis Kathryn Tinkham Candice Rofousse Chris Bellamy Lynn Cornell Carmen LeFaucheurComposite tissues Linda CendalesHeart Patrick BrunevalLiver Jake DemetrisLung William Wallace and Carol FarverPancreasIslets Cinthia Drachenberg and John Papadimitriou

SecretaryTreasurer Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

The World is Changing Rapidly

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

The World is Changing Rapidly

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

The World is Changing Rapidly

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Perfused 7 days without oxygen or nutrients Of course no nuclei seen

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Canadian Data on Public Interest in Regenerative Medicine

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

The Technological

Singularity

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Podocytes go wandering into the interstitium Song et al

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Many problems with stem cell generate

organs not being discussed Do not exclude

yourself from the action in this area

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Many problems with stem cell generate

organs not being discussed Need to get

those conversations to happenThe recellularized organ clots like crazy impossible to

regenerate more than 80 of endothelial surface Artificial heparized surface not fenestrated Cell traffic abnormal

Hard to get right types of cells to right places

Podocytes seems to be terminally differentiated cells when attempt to culture them they turn into different type of cell

Kidney progenitor stem cell difficult to identify kidney work has lagged behind

Easy to make stem cell generated kidneys that lack loop of Henle Could produce lethal polyuria What is ldquofunctionrdquo

Many old fashioned questions of physiology about how the stem cell generated organ works not just true for kidney true for every organ

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Transplant pathologists will also become tissue engineering pathologists pathologists who analyse organs grown from stem cells This is not something beyond us we can adapt to a work life that includes stem cells Someone needs to cross the disciplines

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions intact nephron hypothesis cell regeneration stunned myocardium contraction band necrosis etc Use your nostalgia Stimulate conversations between stem cell researchers and transplant physicians

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Beginning at the Very Beginning

ldquoWe are at the very beginning of time for the human race It is not unreasonable that we grapple with problems But there are tens of thousands of years in the future Our responsibility is to do what we can learn what we can improve the solutions and pass them onrdquo - Richard P Feynman (1918-1988) Physicist Nobel Prize Winner

The sense of the future is behind all good policies Unless we have it we can give nothing either wise or decent to the world - Snow CP (1905-1980) Novelist and Philosopher

To a large extent the future lies before us like a vast wilderness of unexplored reality The God who created and sustained the evolving universe through eons of progress and development has not placed our generation at the tag end of the creative process God has placed us at a new beginning We are here for the future - Sir John Templeton (1912-2008 ) Financial Analyst

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Beginning at the Very Beginning

Like 1851 when the first International Classification of Diseases was presented in the Grand Exhibition of Technology at Londonrsquos Crystal Palace

Emphasis was on cause of death

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Classification focus is on sustaining life

Native and transplanted organ diseases can also occur in tissue engineered organs

The classification focus of the new pathology discipline of Regenerative MedicineTissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death In Regenerative MedicineTissue Engineering Pathology the emphasis is on the degree of normality necessary to sustain life

Normal

Abnormalities of unknown functional significance

Abnormalities which will impair the main functions of the organ

Abnormalities leading to severe organ dysfunction where function may not be great enough to sustain life

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Song et al Interstitium vessels and glomeruli with missing cells

Disordered tubule formation with multiple interconnecting

lumina of differing sizes ldquoCan you really call this a kidneyrdquo (Yes)

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Song et al In addition to missing cells and disordered structures

you have cells in the wrong places Podocytes in the interstitium

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

1 Are there too many missing cells distorted structures for the organ to function adequately

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Focus of Tissue Engineering Pathology The focus of tissue engineering pathology will shift to

the question ldquoIs this organ structurally intact enough to function safely and adequately in the recipientrdquo Using the kidney as an example the specific questions become (Images by Korey Fung)

2 Are there too many cells in the wrong places (eg podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Focus of Tissue Engineering Pathology (Images by Korey Fung)

3 Are there missingdistorted structural elements that represent a risk to the patient (missing loops of Henlecausing lethal polyuria)

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Focus of Tissue Engineering Pathology Using the kidney as an example the specific questions

become

4 Is there too much endothelial disruption

for the organ to be properly perfused

5 What are the risks of neoplastic transformation

Classification categories should be not one-off but reproducible generalizable

Tissue engineering pathology has been up to now really dull since most reports were of scaffolds with no inflammatory reaction Move along nothing to see here pathology but from today becomes really exciting with novel morphological changes and lives hanging in the balance

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Khouloud Saliba and I Presented These Ideas

at TERMIS (Regenerative Medicine) Meeting

in San Diego Dec 11-14 2016

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification

Decellularized Renal Matrix and Regenerative Medicine of the Kidney A Different Point of View Petrosyan Astgik hellip and Perin Laura Tissue Engineering Part B Reviews May 2016 22(3) 183-192

A Step Towards Clinical Application of Acellular Matrix A Clue from Macrophage Polarization Petrosyan A hellipPerin L Matrix Biol 2016 Aug 26 pii S0945-053X(16)30133-0

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification

Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification