A renaissance in renal pathology, nephrology and

transplantation brought about by regenerative

medicine: How to jump start the process  

Kim Solez, MD

Nephrologists & 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.

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 “Banff” – La Coruna, Spain. 2009 Working groups. Meeting in Banff, Alberta, Canada 2013 Establishment of Banff Foundation for Allograft Pathology

BANFF Classification - Milestones

Significance of ‘Banff papers’

• More than 5,000 citations of the 14 Banff meeting reports• 915 Banff / Transplantation papers in PubMed• Banff 2003 meeting report (ABMR criteria) = most cited AJT

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

Tissue Engineering Pathology Added Soon!•

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g, i, t, v - score

The Banff communityPathologistsNephrologistsTx-SurgeonsLab-Medicine

The Banff communityPathologistsNephrologistsTx-SurgeonsLab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

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 membersBiostaticiansMolecular Biologists“Omics”-specialists

New membersBiostaticiansMolecular Biologists“Omics”-specialists

Off-springsLiverPancreasLung, HeartCTA

Off-springsLiverPancreasLung, HeartCTA

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 Chairs: Composite tissues: Linda CendalesHeart : Patrick BrunevalKidney: Mark HaasLiver: Jake DemetrisLung: William Wallace and Carol FarverPancreas: Cinthia Drachenberg

Banff Working Group (BWG) Leads: Molecular 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 committee: Alex 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 FarverPancreas/Islets: Cinthia Drachenberg and John Papadimitriou

Secretary/Treasurer: Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaborationprogress reports to Budged

proposal and accountability for meeting costs

support

BANFF Conferences On Allograft Pathology 1991-Forever?

Rongjia Liu: Consensus Generation in Pathology. (Day

3 Presentation)

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 happen.

The 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 “function”?

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

Banff Foundation for Allograft Pathology and Banff Meetings Must Adapt to Future Changes in Field of Transplantation

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,

It is OK to Allow the Natural Resistance to Change and Nostalgia for the Past to Motivate You!

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! “We 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 on.” - 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 London’s 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 Medicine/Tissue Engineering Pathology is exactly the opposite of traditional classification of disease which starts with causes of death. In Regenerative Medicine/Tissue 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. “Can you really call this a kidney?” (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: “Is this organ structurally intact enough to function safely and adequately in the recipient?” 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: “Is this organ structurally intact enough to function safely and adequately in the recipient?” Using the kidney as an example, the specific questions become: (Images by Korey Fung)

2. Are there too many cells in the wrong places (e.g. podocytes in the interstitium)

Focus of Tissue Engineering Pathology (Images by Korey Fung) 3. Are there missing/distorted structural

elements that represent a risk to the patient? (missing loops of Henle causing 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!

In our original location we had mule deer poking their heads

into the meeting rooms!We’ve come a long way!

Korey Fung: Student involvement in characterizing

the landscape of the new discipline of tissue

engineering pathology: A brave new world in pathology.

Patricia Bacus: A new profession within pathology: Robot liaison/advocate: The best human friend a robot

ever had!

Rich Sutton (UAlberta) Future of AI meeting Puerto Rico Jan

3, 2015

Acceptance. Share power. The AIs will not all be under our control. They will compete and cooperate with us just like other people, except with greater diversity and asymmetries We need to set up mechanisms (social, legal, political, cultural) to ensure that this works out well Inevitably, conventional humans will be less important Step 1: Lose your sense of entitlementStep 2: Include AIs in your circle of empathy

Korey Fung: Student involvement in characterizing

the landscape of the new discipline of tissue

engineering pathology: A brave new world in pathology.