When injected into rats' hearts soon after a heart attack, stem cells taken from human umbilical cord blood (HUCB) greatly reduced the size of heart damage and restored pumping function to near normal. This improvement occurred without the need for drugs to prevent the rats' immune system from rejecting the human cells.
The USF study will be published online this week in the journal Cell Transplantation, accompanied by an editorial discussing the progress of stem cell therapy in treating heart attacks, or myocardial infarctions.
If further animal studies and human clinical trials prove equally successful, the USF researchers suggest that stem cells from umbilical cord blood could be a new, widely applicable treatment for limiting or repairing the heart muscle destroyed when the vital organ's blood supply is cut off. In the United States, nearly one of every 2 men and one of 3 women older than age 40 will suffer a heart attack, leaving them more vulnerable to chronic heart failure or another, potentially fatal, heart attack. Medications and bypass surgery have prolonged the lives of these patients, but many live with heart failure characterized by chronic fatigue and shortness of breath.
"Patients with heart failure due to heart attacks and other causes spend much of their day at home in a chair or in bed. These are the patients whose lives we hope to greatly improve with stem cell therapy to restore heart function," said Dr. Henning, lead author of the study.
"Our initial results are extremely promising, but raise questions about how these umbilical cord blood cells work. Are they transforming into new heart muscle cells or secreting growth factors that trigger the heart to repair itself? We need more research to insure such therapy will ultimately benefit patients with little or no side effects."
"The possibility to regenerate and to restore function of the heart after myocardial infarction with stem cell transplantation holds great promise for treating heart failure," writes David Stern, MD, dean of the Medical College of Georgia, and colleagues in the Cell Transplantation editorial accompanying the USF study. "Additional preclinical animal studies are warranted and should focus on examining the mechanisms that mediate the functional effects of stem cell transplantation."
The USF researchers compared HUBC-treated rats to both untreated rats (those receiving only a sugar water placebo) and control rats with normal hearts. The HUCB stem cells were injected directly into the heart muscle of rats an hour after heart attacks were induced. After four months of recovery, the size of scar tissue left by dead heart muscle was approximately three times smaller in the HUCB treated rats than in the untreated rats. As a result, the heart's pumping capacity improved to near normal in the treated rats, after an initial decline, and was significantly greater than the cardiac function in the untreated rats with heart attacks.
"Scar tissue does not contract," Dr. Henning said. "Since scar tissue was minimized and more heart muscle remained in the treated rats, their hearts were able to function better as pumps."
The USF work adds to a growing field exploring the potential of stem cells to treat ailing hearts. Animal and human cell transplantation to treat heart attacks has focused primarily on immature cells harvested from adult bone marrow and skeletal muscle – with mixed results.
"Although not as primitive as human embryonic stem cells, stem cells isolated from infant's cord blood are less mature than those taken from adult bone marrow and skeletal muscle," Dr. Henning said.
"Cord blood stem cells may be more amenable to repairing hearts. In addition, cord blood stem cells are readily accessible, easy to use, and, like adult stem cells, are not as controversial as embryonic stem cells." said coauthor Paul R. Sanberg, PhD, DSc, director of the USF Center of Excellence for Aging and Brain Repair.
The USF study does not define how the HUCB cells reduced acute heart attack damage in the rats, but the researchers continue to search for explanations. The researchers do not discount transdifferentiation -- that HUCB cells transform into functional heart muscle cells to regenerate damaged tissue. However, Dr. Henning suggests, these stem cells instead may release nourishing substances that rally primitive cells within the heart itself to form new blood vessels and muscle.
Other authors of the study were Hamdi Abu-Ali; MD; John Balis, MD; Michael B. Morgan, MD; and Alison E. Willing, PhD. The USF study was supported by the American Heart Association, the Veterans Administration, a Florida Biomedical Research Grant, and Saneron CCEL Therapeutics, Inc., a USF spin-out biotechnology company focusing on developing stem cell therapies for debilitating or deadly diseases. Some study authors are affiliated with Saneron and are co-inventors on related patent applications by USF.
Journal
Cell Transplantation