Clinical Studies Show Stem Cell Line is Effective
Building on a trailblazing body of work in stem cell research at the University of Miami Miller School of Medicine, an interdisciplinary team led by Joshua M. Hare, M.D., Director of the Interdisciplinary Stem Cell Institute, revealed the results of two pioneering studies in cardiac stem cell therapy during oral presentations at the American Heart Association national convention held in Dallas November 18 and 19.
Both studies build on Hare’s scientific and clinical research in the field of cardiac stem cell therapy. “The results of these studies,” said Hare, Chief Science Officer at the Miller School, “show that mesenchymal stem cells can have a major impact on cardiac care.”
The first study, “Transendocardial Autologous Cells in Ischemic Heart Failure (TAC-HFT),” was presented as it was simultaneously published in The Journal of the American Medical Association (JAMA). One of three clinical trials studying stem cells for the treatment of heart failure completed by Hare’s team since 2008, TAC-HFT is the first and only study in the nation to compare two types of stem cells: whole bone marrow or mesenchymal stem cells (MSC), which are derived from adults’ bone marrow.
Alan W. Heldman, M.D., professor of medicine and lead author of the TAC-HFT study, used a catheter with a helical-shaped needle tip to inject stem cells directly into the heart muscle of patients whose heart function had been weakened by a prior heart attack. Heldman injected either the patient’s whole bone marrow, the patient’s own mesenchymal stem cells that had been cultured in the laboratory, or placebo. Sixty-five patients were enrolled in the Miller School double-blind study that examined the safety and efficacy of these stem cells in patients with ischemic cardiomyopathy (ICM).
Describing the results, Heldman said, “Mesenchymal stem cell therapy reduced the size of the heart attack scar, and increased patients’ exercise capacity and improved their quality of life. Comparing the mesenchymal stem cells to bone marrow cells and to placebo leads us to hypothesize that the mesenchymal stem cells are a more potent treatment. We were also very pleased to find no safety concerns with the new therapy.”
Patients who received bone marrow cells also showed some improvement in quality of life. “Based on the results of this rigorous study,” said Hare, “we hypothesize that the mesenchymal stem cells may become a revolutionary new treatment for patients with congestive heart failure. The goal now is to examine whether that holds up in a larger sample.”
A second study presented, the PROMETHEUS study, shows that patients can also benefit from MSC injections at the time of cardiac surgery.
“What Josh, Alan and their team have accomplished in the last five years is extraordinary,” said Pascal J. Goldschmidt, M.D., Senior Vice President for Medical Affairs and Dean of the Miller School. “They are true pioneers, whose vision will result in effective treatments for countless patients worldwide. No other center in the nation has performed this many cardiac stem cell trials.” Since 2008, Hare and his team have completed and published three clinical trials, enrolling the most patients anywhere in the U.S.
Joel E. Fishman, M.D., Ph.D., professor of radiology and co-author of the study, led the advanced imaging used to ascertain patient results. “It’s clear that CT scanning has a vital role in determining the efficacy of stem cell therapy,” said Fishman. “With it, we were able to evaluate multiple aspects of cardiac structure, tissue, and function with a very high degree of accuracy.”
“Using CT scanning and MRI to determine efficacy,” said Eduard Ghersin, M.D., associate professor of radiology and study co-author, “further enhanced our ability to determine the potential of stem cell therapy as a viable treatment option.”
One attractive element of mesenchymal stem cells is their ability to differentiate into a variety of cell types. Using a patient’s own mesenchymal cells requires removing bone marrow, then separating and enhancing the mesenchymal cells over several weeks.
Hare said the next step with mesenchymal cells is to determine whether autologous (the patient’s own) or allogeneic (from a donor) cells are the best treatment. “We’ve already shown in a small trial that allogeneic cells are as safe and effective as autologous. We think that’s where the field is heading.”
The PROMETHEUS trial, presented in oral sessions, was the first stem cell trial Hare and his team started at the Miller School in 2008. In it, eight patients who had suffered a myocardial infarction were injected with their own (autologous) mesenchymal stem cells during open heart surgery. This trial was presented by post-doctoral fellow Vasilieos Karantalis, M.D.
“The effects were dramatic,” said Hare, who is also Louis Lemberg Professor of Medicine. “We discovered the cells work at the site of injection.” The study found that the cells promoted the formation of new blood vessels and new cardiac muscle that beats and reduced scar tissue from the infarction. The findings also have merit because they provide further evidence that the cells perform as predicted based on their biological features, thus confirming their potential as an effective cell therapy line.
This work “has the potential to significantly augment what we offer to cardiac patients,” said James F. Symes, M.D., professor of surgery at the Miller School and Chief of Cardiovascular and Thoracic Surgery at the Miami VA Healthcare System, who was part of the surgical team of this study. “While it’s an early study, the results indicate that stem cell therapy can offer hope to countless patients who are not candidates for a surgical approach.”
Mauro Moscucci, M.D., M.B.A., Professor and Interim Chair of Medicine, and Chief of the Cardiovascular Division, said he expects “to see a paradigm shift in how we approach patients with heart disease. The work of Josh and his team is opening new doors, and could transform the care of cardiac patients in the near future.”
One year after presenting another late-breaking and widely reported trial at the AHA demonstrating that allogeneic mesenchymal stem cells are as effective as autologous, Hare is looking to the future. He and his team have received approval from the Food and Drug Administration to perform a study that examines the efficacy of combining a patient’s cardiac stem cells with their own mesenchymal stem cells. They are also embarking on a host of new studies aimed at advancing the care of patients with heart, vascular and pulmonary diseases.
The TAC-HFT study was supported, in part, by a grant from the National Heart, Lung, and Blood Institute’s Specialized Center for Cell Therapy, and Biocardia, Inc., maker of the Helical Infusion Catheters.