Both cell types were found to work safely and with similar effectiveness. Donor cells were not rejected by the patients’ immune systems. Delivered in a minimally invasive procedure similar to a cardiac catheterization, the cells were shown over time to reduce the amount of damaged tissue by 33 percent, overturning a long-held medical belief that damaged cardiac tissue could not be repaired.
The findings, “Comparison of Allogeneic vs. Autologous Bone Marrow Derived Mesenchymal Stem Cells Delivered by Transendocardial Injection in Patients with Ischemic Cardiomyopathy: The POSEIDON Randomized Trial,” led by Joshua M. Hare, M.D., Director of the Interdisciplinary Stem Cell Institute (ISCI), are simultaneously being published in the November 6 edition of the Journal of the American Medical Association and presented at the American Heart Association’s Scientific Sessions 2012 in Los Angeles.
“In many cases we observed clinically significant improvement,” said Hare, the Louis Lemberg Professor of Medicine in the Cardiovascular Division. “Even in patients who had heart attacks several decades before treatment, both donor and recipient stem cells reduced the amount of scarring substantially.”
“What Josh and his team have demonstrated is nothing short of groundbreaking,” said Pascal J. Goldschmidt, M.D., Senior Vice President for Medical Affairs and Dean of the Miller School, and CEO of UHealth. “These study results are further proof that the basic science and translational work being done at the Interdisciplinary Stem Cell Institute is paving the way for regenerative medicine.”
Mesenchymal stem cells (MSCs) are found in adults’ bone marrow. The use of donor cells was possible because these cells are not attacked by the body’s protective antibodies. Cells were separated from other tissue and grown in a laboratory setting before being administered to patients.
Previous studies indicated that MSCs might improve heart muscle function in patients with heart scarring from a prior heart attack. Heart muscle weakening from such scars (ischemic cardiomyopathy) is the most common cause of debilitating and deadly congestive heart failure.
The 13-month Phase I/II trial, funded by the National Heart, Lung, and Blood Institute at the National Institutes of Health, is the first ever to directly compare the safety and efficacy of mesenchymal stem cells taken from patients with those provided by a donor. Thirty patients with chronic ischemic cardiomyopathy received various doses of MSCs. Half received their own stem cells, while the other half received donor stem cells. The study results suggest that using donor cells may speed up treatment.
“Patients who received the cell therapy clearly benefitted and the cells from donors are just as safe as those from the recipient,” said Hare. In order to regenerate new heart muscle with MSCs, large amounts of the cells must be grown, which takes six to eight weeks.
Alan W. Heldman, M.D., professor of medicine and co-author of the study who performed the injection procedures, said, “Discovering that the donor cells are as safe and effective as the recipient cells opens up a new door in potential therapy. Ideally, we could bank donor cells and use them immediately on patients, as needed.” The stem cells were delivered directly into the damaged area of patients’ heart muscle using a catheter with a needle tip. “An additional important finding was the safety of this new cardiac catheterization technique,” said Heldman.
“This trial shows that using mesenchymal stem cells, taken from either patients themselves or from donors, is safe, which gives us confidence in planning larger trials,” said Denis Buxton, Ph.D., associate director of the Basic and Early Translational Research Program, Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute. “If future studies show similar safety and efficacy, patients with ischemic cardiomyopathy may have a treatment option beyond medical management.”
“This work is an outstanding step forward in proving that cell therapy has enormous potential,” said Mauro Moscucci, M.D., M.B.A., Professor and Interim Chair of Medicine, and Chief of the Cardiovascular Division. “As cardiologists, we have all been taught that damaged heart tissue cannot be repaired. Josh and Alan’s findings change that thinking. Because of this work, cell therapy may one day be part of a cardiologist’s armamentarium, just as stenting and other minimally invasive procedures are now.”
Joel E. Fishman, M.D., professor of radiology, and co-author of the study, emphasized the importance of advanced heart imaging in stem cell research. “Our use of CT scanning before and after stem cell therapy allowed us to measure heart size, function and cardiac muscle health with a very high degree of accuracy.”
The results hold great promise for millions of cardiology patients, said the Director of Research and co-author, Darcy L. DiFede Velazquez, RN, B.S.N. “If the results of our work continue to hold up in future studies, by using MSCs to repair heart muscle, we can dramatically improve the quality of life for patients who before now had few options.”
Next, Hare and his colleagues are planning a larger, placebo-controlled trial to determine whether MSCs can become standard therapy for ischemic cardiomyopathy and congestive heart failure.
Co-authors of the study include Viky Y. Suncion, M.D., post-doctoral associate; Eduard Ghersin, M.D., associate professor of radiology; Ivonne H. Schulman, M.D., associate professor of medicine; John J. Byrnes, M.D., professor of medicine; Maureen H. Lowery, M.D., professor of medicine; Phillip Ruiz, M.D., professor of surgery; Alexandra Amador, laboratory manager for histocompatibility; and Jose da Silva, Ph.D., associate scientist and cGMP laboratory manager. Researchers at the Johns Hopkins University School of Medicine also collaborated on the study.
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