Heart muscle cells grown from human embryonic stem cells can help repair damaged hearts following a heart attack. August 30, 2007

August 30, 2007 By Benjamin A. Olenchock, M.D. Ph.D. [mailto:bolenchock@partners.org]

Seattle, WA

Researchers at the University of Washington and Geron Corporation have successfully engrafted heart muscle cells (cardiomyocytes) derived from human embryonic stem cells (ES) into a rat heart after a heart attack. The transplanted cells helped to improve the function of the injured heart.

Previous research had demonstrated successful engraftment of cardiomyocytes grown in vitro from human ES cells into a healthy rat heart. Engraftment into an area of an infarct, however, proved to be more difficult. The solution to this problem was a cocktail of pro-survival factors, which the researchers developed through rational design and a series of trials and errors. The so-called Pro-Survival Cocktail (PSC) comprised a cell-permeant peptide from Bcl-XL (an anti-apoptotic protein), cyclosporine A (an immunosuppressant), Matrigel (a platform for cell adherance), pinacidil (a potassium channel agonist), IGF-1 (a growth factor), and ZVAD-fmk (a cell death inhibitor).

The PSC was very successful in improving graft success rate after heart attacks. The grafts delivered in the presence of PSC were small, but were four-times larger than grafts without PSC. The grafted cardiomyocytes helped to preserve left ventricular end-systolic diameter, and to a lesser extent left ventricular end diastolic diameter. As a result, fractional shortening and ejection fraction were also more preserved in rats that received the allografts after a heart attack.

The use of human ES cells to treat disease has been a hotbed of controversy. Moral and political issues, special interests groups, and overblown promises of miracle cures occasionally overshadow innovative and careful research such as this. The researchers were blinded to the treatment groups and they demonstrated a modest effect on a meaningful measure of heart function. The findings were reproducible, statistically significant, and suggest that if engraftment can be achieved, this therapy could improve the function of damaged hearts.

Geron corporation funded this research and plans to move this therapy into larger animal models and eventually into the clinic. The transition into the clinics will involve scaling many obstacles such as cellular immunity and individual variations in responses to treatment. Nonetheless, their findings, published in the journal Nature Biotechnology, mark a major step forward towards the use of human ES cells for tissue replacement in adults.


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