Over 5 million Americans suffer with congestive heart failure, and 500,000 new cases are diagnosed each year. Unfortunately, these numbers are likely to worsen over the next two decades, as the total number of heart failure patients is expected to rise by over 50%. Ischemic heart disease is the most common cause of heart failure, and stem cell transplantation may represent the first realistic clinical strategy for actually reversing the deleterious effects of what has been considered irreversible damage to the heart resulting from myocardial infarction. However, significant hurdles must still be overcome before successful human translation of this strategy can be realized; in particular, a means is needed both for preventing the rapid death of most of the transplanted cells and for encouraging their functional contribution to the heart. We propose a strategy, termed Matrix-Assisted Cell Transplantation (MACT), that has been developed by a collaboration of bioengineers and cardiac surgeons/cell biologists to improve the efficacy of stem cell transplantation into a heart injured by MI. This strategy is based upon novel biomimetic polymers that will: 1) provide a foundation for increased stem cell survival, and 2) enhance the functional capacity of transplanted stem cells in an animal model of MI. The goal of our research proposal is to establish artificial extracelluar matrices that enhance the survival and performance of cells transplanted into ischemically damaged heart muscle and that, within a 4 year period, can begin pre-clinical testing for preservation of cardiac function and prevention of post-MI heart failure.
The proposed research will benefit California by preserving and strengthening California’s position as a leader in the emerging field of human stem cell therapeutics. Through the recent passage of Proposition 71, the voters of California have identified stem cell research as a key area of focus for the state, with anticipated positive impacts including: creation of biotechnology jobs, attraction of leading researchers to Californian universities, creation of valuable intellectual property, and advancement of therapeutics beneficial to California’s residents. This proposal will bring California’s diverse technical resources to bear towards this goal by combining the expertise of leading academics in the fields of biomaterials and bioengineering with world-leading clinicians to the field of human embryonic stem cell therapeutics. The use of the synthetic matrices developed in this collaboration for the manufacture of hESC-derived cell therapeutics will increase the potential availability of such treatments to patients, while at the same time reducing the risk of zoonoses from such therapies. More than 2 million Californians stand to benefit from development of hESC-based therapies in our program of heart failure treatment, many more could be affected by the translation of our technology to similar therapies for additional degenerative disorders such as Parkinson’s disease, Alzheimer’s disease, diabetes, rheumatoid arthritis and osteoporosis.