Unique trial studying stem cells’ effect on heart damage launches at UF Health
For the first time ever, University of Florida Health researchers are evaluating whether or not the combination of heart and bone marrow stem cells can repair heart damage.
The first patient in the clinical trial, who has had several heart attacks and other cardiac issues, received the stem cell mixture during a procedure in June, said Carl J. Pepine, M.D., a professor in the UF College of Medicine’s department of medicine.
While other research has focused on the effectiveness of either heart or bone marrow stem cells, Pepine said the recent procedure is the first time anywhere in the world that the combination of these two cell types has been used together in a heart patient. Pepine said the clinical trial is testing whether or not the heart and bone marrow stem cells will be more effective together than individually. The cardiac stem cells are meant to eventually regenerate heart muscle, while the bone marrow mesenchymal stem cells have the ability to generate blood vessels and supportive tissue for heart cells.
The patient who received the dual stem cells is part of a pilot stage involving 18 other participants, some of whom were randomly assigned to the standard of care group. Standard of care treatment includes lifestyle modification and three cardiac-related medications: a beta blocker, an angiotension-converting enzyme inhibitor and an aldosterone blocker. In November, federal regulators will review the results and decide whether or not to approve a larger trial or order modifications. Ultimately, Pepine said they hope to test the dual stem cells’ comparative effectiveness in a double-blind randomized, controlled trial involving 144 participants. During this next stage of the project, four groups of 36 patients each would receive either the combination of stem cells, only the bone marrow or heart stem cells alone, or a placebo.
“We’re trying to learn if we can improve heart function as well as the patient’s ability to stay out of the hospital,” he said.
The treatment being studied started with stem cells being extracted from the patient’s heart and bone marrow and cultured for about four months to increase the number of cells before being implanted, Pepine said.
Implanting the cells in the heart’s left ventricle is an exceedingly precise, two stage-process: An electrode with mapping capability is used inside the heart’s main pumping chamber to pinpoint 20 to 30 areas of heart tissue with adequate electrical voltage. Then, Pepine and his colleagues choose sites where they believe damaged heart tissue has the potential to recover with the correct stem cell treatment. Using a small-needle tipped catheter, about 15 injections of stem cells are made in the left ventricle — for a total of at least 1 million cells.
Within days, most of the stem cells are flushed from the heart, but it is believed they leave behind beneficial material or foster conditions that promote heart muscle regeneration, according to Pepine.
“The thinking is that this will set into motion some type of reaction that will perpetuate itself, attract more stem cells to the damaged area and result in sustained improvement over time,” he said.
During the larger trial, participants who receive the stem cell duo will be compared with those who only receive only one kind of stem cell or a placebo at intervals of three months, six months and one year.
Injecting the cells at the correct sites is the job of R. David Anderson, M.D., an interventional cardiologist and professor in the department of medicine’s division of cardiovascular medicine.
“What everyone would like to see is improvements in left-side heart function. We’ve already proven the safety of the cell delivery procedure. What we need to do now is find the right cell combination, the right dose and maybe still even improve the delivery method. Once we optimize all those things, we hope we’ll get close to hitting a home run,” Anderson said.
Cardiovascular stem cell therapy requires a team of specialized experts for cell harvesting, processing and implantation, nursing care and anesthesia, Pepine said. In addition to Pepine and Anderson, the team includes Mustafa Ahmed, M.D., an assistant professor of medicine; Juan M. Aranda Jr., M.D., a professor of medicine; Nikolaus Gravenstein, M.D., the Jerome H. Modell professor of anesthesiology in the department of anesthesiology; Dana Leach, D.N.P., associate director of cardiology clinical trials; Emma Hall Rosenau, M.P.H., research programs coordinator; and clinical research coordinators Sarah Long, B.S.N., and Nicole Bostick, cardiology research coordinator.
The trial is sponsored by the National Heart, Lung, and Blood Institute’s Cardiovascular Cell Therapy Network, which is a part of the National Institutes of Health.
Pepine is also leading several other clinical trials that are the first of their kind. An upcoming study will use mesenchymal stem cells to potentially repair heart damage caused by chemotherapy drugs. A second trial is evaluating whether stem cell therapy can be used to develop blood vessels in the legs, where peripheral artery disease can cause reduced circulation and make walking painful. Those results are expected to be reported at an American Heart Association meeting in November.