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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] September 7, 2005
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 Aaron B. Baker May 18th, 2015 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 Aaron B. Baker Bioengineering and Therapeu3cs May 18th, 2015 Regenera3ve Medicine: Not a New Dream Laboratory for Cardiovascular Bioengineering and Therapeu3cs The Fountain of Youth, Lucas Cranach (1546) Aaron B. Baker May 18th, 2015 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 Aaron B. Baker May 18th, 2015 Regenera3ve Medicine Applica3ons Organ Repair: •  Myocardial Regen. •  Skeletal muscle repair •  Wound healing Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 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 Aaron B. Baker May 18th, 2015 Why it won’t go away! Patients Diagnosed w/ Diabetes
Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 Hope from Nature: the Natural Bypass Laboratory for Cardiovascular http://circ.ahajournals.org/content/116/11/e340.full
Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 Technologies and Innova-ons that will Shape the Future of Medicine! Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 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 Aaron B. Baker May 18th, 2015 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 Aaron B. Baker May 18th, 2015 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 f-or Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 Bioengineered Endothelial Cells Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 Cell Therapy with Vascugel AV Fistula for
Vascular Access for
Dialysis
Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 Vascular Access Stays Open Longer Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 Tissue Engineered Bladder: First Engineered Organ in Clinical Trials Dr. Anthony Atala
Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 Stem Cells Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 Stem Cell Therapy for Heart AXack Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 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 Aaron B. Baker May 18th, 2015 Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 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 •  D o u b t s a b o u t t h e e x e c u - o n o f t h e science/trials Laboratory for Cardiovascular Bioengineering and Therapeu3cs “Francis’s team identified more
than 600 discrepancies, including
contradictory claims for how
patients were randomized,
conflicting data in figures and
tables, and statistically impossible
May 18th, 2015 Aaron B. Baker results..”
Induced Pluripotent Stem Cells Laboratory for Cardiovascular Aaron B. Baker Hochedlinger,K and Plath, K. Development 136, 509-523
(2009)
Bioengineering and Therapeu3cs The Nobel Prize in Physiology or Medicine
2012:
May 18th, 2015 John B. Gurdon and Shinya Yamanaka
iPS Cell-­‐Derived Cardiomyocytes • 
hbps://www.youtube.com/watch?v=7GVLMcvvQ4w Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 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 Aaron B. Baker May 18th, 2015 Example: Teratomas with iPS Cell Injec3on Cartilage
Skin
Intestine
Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 Many Poten3al Uses For iPS Cells Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 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 Aaron B. Baker May 18th, 2015 Technology 2. Organotypic Assays Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 Why this is Huge: Drug Development Cost have Skyrocketed! Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 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 Aaron B. Baker May 18th, 2015 Drug Discovery Pipeline Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 Organotypic Lung-­‐on-­‐a-­‐Chip Assay Laboratory for Cardiovascular B. Baker D. Huh, et al, A Human Disease Model of Drug Toxicity–Induced Aaron Pulmonary
Edema in a Lung-on-a-Chip Microdevice.
Bioengineering a
nd T
herapeu3cs Sci. Transl. Med. 4, 159ra147 (2012).
May 18th, 2015 Organotypic Screening Assays Laboratory for Cardiovascular B. Baker D. Huh, et al, A Human Disease Model of Drug Toxicity–Induced Aaron Pulmonary
Edema in a Lung-on-a-Chip Microdevice.
Bioengineering a
nd T
herapeu3cs Sci. Transl. Med. 4, 159ra147 (2012).
May 18th, 2015 Organotypic Screening Assays Laboratory for Cardiovascular B. Baker D. Huh, et al, A Human Disease Model of Drug Toxicity–Induced Aaron Pulmonary
Edema in a Lung-on-a-Chip Microdevice.
Bioengineering a
nd T
herapeu3cs Sci. Transl. Med. 4, 159ra147 (2012).
May 18th, 2015 Drug Screening For Cancer with Mechanical Microenvironments Figure 14.17b The Biology of Cancer (© Garland Science 2007)
Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 Technology 3. Rapid 3D Manufacturing Bioprinted Heart Valve
Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker https://www.asme.org/engineering-topics/articles/bioengineering/creating-valve-tissue-using-3d-bioprinting
May 18th, 2015 3D Printers •  Inkjet Bioprin-ng •  Microextrusion Bioprin-ng •  Laser Assisted Bioprin-ng Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 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 Aaron B. Baker May 18th, 2015 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 Aaron B. Baker May 18th, 2015 PaXerning 3D Vascular Networks Laboratory for Cardiovascular Aaron B. Baker http://www.nature.com/nmat/journal/v11/n9/full/nmat3357.html
Bioengineering and Therapeu3cs May 18th, 2015 PaXerning 3D Vascular Networks Laboratory for Cardiovascular Aaron B. Baker http://www.nature.com/nmat/journal/v11/n9/full/nmat3357.html
Bioengineering and Therapeu3cs May 18th, 2015 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 Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015 Thank you! Laboratory for Cardiovascular Bioengineering and Therapeu3cs Aaron B. Baker May 18th, 2015