Innovations and Challenges in a New Era of Translational Medicine

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



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



Regenera3ve Medicine: Not a New Dream

The Fountain of Youth, Lucas Cranach (1546)



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



Regenera3ve Medicine Applica3ons

Organ Repair: • Myocardial Regen. •  Skeletal muscle repair • Wound healing



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



Why it won’t go away!

Patients Diagnosed w/ Diabetes



Hope from Nature: the Natural Bypass

http://circ.ahajournals.org/content/116/11/e340.full



Technologies and Innova-ons that will Shape the Future of Medicine!



Technology 1. Cell Based Therapies

•  Adult Cells or Stem Cells from Pa-ent – Harvested and expanded in vitro –  Injected or implanted to treat disease



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



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!



Bioengineered Endothelial Cells



Cell Therapy with Vascugel

AV Fistula for Vascular Access for

Dialysis



Vascular Access Stays Open Longer



Tissue Engineered Bladder: First Engineered Organ in Clinical Trials

Dr. Anthony Atala



Stem Cells



Stem Cell Therapy for Heart AXack



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..







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..”



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



iPS Cell-‐Derived Cardiomyocytes

•  hbps://www.youtube.com/watch?v=7GVLMcvvQ4w



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.



Example: Teratomas with iPS Cell Injec3on

Cartilage

Intestine

Skin



Many Poten3al Uses For iPS Cells



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



Technology 2. Organotypic Assays



Why this is Huge: Drug Development Cost have Skyrocketed!



ROI has Diminished Drama3cally! R&D Expenditures and Return on Investment: A Declining Function

Phrma (2005); Tufts CSDD (2005)



Drug Discovery Pipeline



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).



Organotypic Screening Assays




Organotypic Screening Assays




Drug Screening For Cancer with Mechanical Microenvironments

Figure 14.17b The Biology of Cancer (© Garland Science 2007)



Technology 3. Rapid 3D Manufacturing

https://www.asme.org/engineering-topics/articles/bioengineering/creating-valve-tissue-using-3d-bioprinting

Bioprinted Heart Valve



3D Printers

•  Inkjet Bioprin-ng • Microextrusion Bioprin-ng

•  Laser Assisted Bioprin-ng



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



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



PaXerning 3D Vascular Networks

http://www.nature.com/nmat/journal/v11/n9/full/nmat3357.html



PaXerning 3D Vascular Networks

http://www.nature.com/nmat/journal/v11/n9/full/nmat3357.html



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



Thank you!

Innovations and Challenges in a New Era of Translational Medicine

Documents