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September 7, 2005
The Future is Now: Innova3ons and Challenges
in a New Era of Transla3onal Medicine
MLA 2015 Conference
Aaron B. Baker, Ph.D. Department of Biomedical Engineering
University of Texas at Aus3n [email protected]
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Overview
• What is regenera-ve medicine?
• Why is it needed?
• Three technologies that will change the
future of medicine!
– Where are we now?
– Challenges and hope for the future
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Regenera3ve Medicine
• Overall goal is to create technology and therapies that repair or replace damaged or diseased tissues and organs
• Current therapies focus on preserving remaining tissue and minimizing damage
• Many approaches – Tissue engineering – Biologics – Cell Therapies
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Regenera3ve Medicine: Not a New Dream
The Fountain of Youth, Lucas Cranach (1546)
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Regenera3ve Medicine Applica3ons
Ar3ficial Organs: • 117,521 people in United States
• ~18 people die every day wai-ng
• Synthe-c blood products
• Ar-ficial pancreas for diabetes
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Regenera3ve Medicine Applica3ons
Organ Repair: • Myocardial Regen. • Skeletal muscle repair • Wound healing
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Massive Need for Regenera3ve Therapies in Cardiovascular Medicine
• Accumula-on of lipids, calcium, ECM and prolifera-ng cells
• Chronic, complex disease • Build up of plaque in arteries that can block blood flow
• Plaques can rupture to cause sudden blockages
• Ischemia: lack of blood flow to a -ssue
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Why it won’t go away!
Patients Diagnosed w/ Diabetes
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Hope from Nature: the Natural Bypass
http://circ.ahajournals.org/content/116/11/e340.full
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Technologies and Innova-ons that will Shape the Future of Medicine!
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Technology 1. Cell Based Therapies
• Adult Cells or Stem Cells from Pa-ent – Harvested and expanded in vitro – Injected or implanted to treat disease
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Technology 1. Cell Based Therapies
• Adult Cells or Stem Cells from Pa-ent – Harvested and expanded in vitro – Injected or implanted to treat disease
• Many applica-ons feel close to transla-on – Type I diabetes transplant of new pancreas cells – Adult stem cells for heart disease – Neuronal transplants for Parkinson’s disease – Bone marrow transplant for various blood cancers – Muscular dystrophy and polio
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
AV Fistula for Vascular Access for Dialysis
- 400,000+ people on dialysis in the U.S. - About 40% of AV Fistula fail within 18 months!
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Bioengineered Endothelial Cells
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Cell Therapy with Vascugel
AV Fistula for Vascular Access for
Dialysis
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Vascular Access Stays Open Longer
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Tissue Engineered Bladder: First Engineered Organ in Clinical Trials
Dr. Anthony Atala
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Stem Cells
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Stem Cell Therapy for Heart AXack
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
CMR shows that CSC infusion produces a striking improvement in both global and regional LV
func3on, a reduc3on in infarct size, and an increase in viable 3ssue that persist at least 1 year and are consistent with
cardiac regenera3on.
Mul3ple clinical trials started..
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
A Lot of Early Hope but Some Setbacks
• Early trials using bone-‐marrow derived stem cells showed promise
• Some later trials and large animal studies did not show improvement
• Doub t s a b o u t t h e e x e c u - o n o f t h e science/trials
“Francis’s team identified more than 600 discrepancies, including contradictory claims for how p a t i e n t s w e r e r a n d o m i z e d , conflicting data in figures and tables, and statistically impossible results..”
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Induced Pluripotent Stem Cells
Hochedlinger,K and Plath, K. Development 136, 509-523 (2009) The Nobel Prize in Physiology or Medicine 2012:
John B. Gurdon and Shinya Yamanaka
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
iPS Cell-‐Derived Cardiomyocytes
• hbps://www.youtube.com/watch?v=7GVLMcvvQ4w
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Balancing Regenera3on and Cancer
There is inherent risk in encouraging -ssues to grow and/or adding cells that do not die or are recognized by the immune system.
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Example: Teratomas with iPS Cell Injec3on
Cartilage
Intestine
Skin
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Many Poten3al Uses For iPS Cells
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Technology 2. Organotypic Assays
• Organ-‐on-‐a-‐Chip Assays – Reduce difference with in vivo studies – Reduce need for animal studies – Accelerate pathway discovery and drug screening
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Technology 2. Organotypic Assays
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Why this is Huge: Drug Development Cost have Skyrocketed!
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
ROI has Diminished Drama3cally! R&D Expenditures and Return on Investment: A Declining Function
Phrma (2005); Tufts CSDD (2005)
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Drug Discovery Pipeline
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Organotypic Lung-‐on-‐a-‐Chip Assay
D. Huh, et al, A Human Disease Model of Drug Toxicity–Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice. Sci. Transl. Med. 4, 159ra147 (2012).
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Organotypic Screening Assays
D. Huh, et al, A Human Disease Model of Drug Toxicity–Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice. Sci. Transl. Med. 4, 159ra147 (2012).
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Organotypic Screening Assays
D. Huh, et al, A Human Disease Model of Drug Toxicity–Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice. Sci. Transl. Med. 4, 159ra147 (2012).
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Drug Screening For Cancer with Mechanical Microenvironments
Figure 14.17b The Biology of Cancer (© Garland Science 2007)
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Technology 3. Rapid 3D Manufacturing
https://www.asme.org/engineering-topics/articles/bioengineering/creating-valve-tissue-using-3d-bioprinting
Bioprinted Heart Valve
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
3D Printers
• Inkjet Bioprin-ng • Microextrusion Bioprin-ng
• Laser Assisted Bioprin-ng
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
One Approach for Bioprin3ng
• Uses bioink, mixture of stem cells • Printer moves back and forth dropping out one bioink par-cle at
a -me to form one layer • Printer prints out one layer of cells
at a -me on biopaper, which is made up of collagen, water, and hydrogels
• Layers are printed one top of each other
• Ajer cells fuse, biopaper is removed
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Why this is a Game Changer
• Advantages – Put together complex organs with mul-ple cell types – Print pa-ent’s own cells – Personalized organ size and geometry – 3D paberning
• Challenges – Resolu-on: hard to print soj materials accurately – Cell viability – Cost – Vasculariza6on
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
PaXerning 3D Vascular Networks
http://www.nature.com/nmat/journal/v11/n9/full/nmat3357.html
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
PaXerning 3D Vascular Networks
http://www.nature.com/nmat/journal/v11/n9/full/nmat3357.html
Laboratory for Cardiovascular Bioengineering and Therapeu3cs
May 18th, 2015 Aaron B. Baker
Overall Summary
Several technologies are poised to have synergis-c contribu-ons to medicine and drug discovery! – iPS cells to powerfully control cell behavior – Organotypic screening assays to accelerate discovery and drug development
– 3D bioprin3ng to enable the spa-al control