Stem cells are proving themselves beneficial once again after scientists used the controversial building blocks to resurrect dead, scarred heart muscle damaged by recent heart attack.
Results from a Cedars-Sinai Heart Institute clinical trial show that treating heart attack patients with an infusion of their own heart-derived cells helps damaged hearts re-grow healthy heart muscle.
Reporting in The Lancet medical journal, the researchers said this is the clearest evidence yet that broken hearts can heal. All that is needed is a little help from one´s own heart stem cells.
“We have been trying as doctors for centuries to find a treatment that actually reverses heart injury,” Eduardo Marban, MD, PhD, and lead author of the study, told WebMD. “That is what we seem to have been able to achieve in this small number of patients. If so, this could change the nature of medicine. We could go to the root of disease and cure it instead of just work around it.”
Marban invented the “cardiosphere” culture technique used to create the stem cells and founded the company developing the treatment.
“These findings suggest that this therapeutic approach is feasible and has the potential to provide a treatment strategy for cardiac regeneration after [heart attack],” wrote University of Hong Kong researchers Chung-Wah Siu and Hung-Fat Tse in an accompanying editorial of Marban´s paper.
The British Heart Foundation told James Gallagher of BBC News that this could “be great news for heart attack patients” in the future.
A heart attack occurs when the heart is starved of oxygen, such as when a clot is blocking the blood flow to the organ. As the heart heals, the dead muscle is replaced by scar tissue, which does not beat like heart muscle. This in turn reduces the hearts ability to pump blood around the body.
Doctors have long been searching for ways to regenerate damaged heart muscle, and now, it seems heart stem cells are the answer. And the Cedars-Sinai trial was designed to test the safety of using stem cells taken from a heart attack patient´s own heart.
The researchers found that one year after receiving the treatment, scar size was reduced from 24 percent to 12 percent of the heart in patients treated with heart stem cells. Patients in the control group, who did not receive stem cells, did not experience a reduction in their heart attack scar tissues.
“While the primary goal of our study was to verify safety, we also looked for evidence that the treatment might dissolve scar and re-grow lost heart muscle,” Marban said in a statement. “This has never been accomplished before, despite a decade of cell therapy trials for patients with heart attacks. Now we have done it. The effects are substantial, and surprisingly larger in humans than they were in animal tests.”
“These results signal an approaching paradigm shift in the care of heart attack patients,” said Shlomo Melmed, MD, dean of the Cedars-Sinai medical faculty and the Helene A. and Philip E. Hixon Chair in Investigative Medicine. “In the past, all we could do was to try to minimize heart damage by promptly opening up an occluded artery. Now, this study shows there is a regenerative therapy that may actually reverse the damage caused by a heart attack.”
Marban cautioned that stem cells do not do what people generally think they do. The general idea has been that stem cells multiply over and over again, and, in time, they turn themselves and their daughter cells into new, working heart muscle.
But Marban said the stem cells are actually doing something more amazing.
“For reasons we didn´t initially know, they stimulate the heart to fix itself,” he told Daniel J. DeNoon of WebMD. “The repair is from the heart itself and not from the cells we give them.”
Exactly how the stem cells invigorate the heart to do this was a matter of “feverish research” in the lab.
The CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) clinical trial was part of a Phase I study approved by the US Food and Drug Administration (FDA) and supported by the National Heart, Lung, and Blood Institute.
Marban used 25 volunteer patients who were of an average age of 53 and had recently suffered a heart attack that left them with damaged heart muscle. Each patient underwent extensive imaging scans so doctors could pinpoint the exact location and severity of the scars. Patients were treated at Cedars-Sinai in LA and at Johns Hopkins Hospital in Baltimore.
Eight of the 25 patients served as a control group, receiving conventional medical treatment. The other 17 patients who were randomized to receive the stem cell treatments underwent a minimally invasive biopsy, under local anesthesia. Using a catheter inserted through a vein in the neck, doctors removed a small sample of heart tissue, about half the size of a raisin. The heart tissue was then taken to the lab at Cedars-Sinai and cultured and multiplied the cells using specially developed tools.
The doctors then took the multiplied heart-derived cells — roughly 12 million to 25 million of them per patient — and reintroduced them into the patient´s coronary arteries during another minimally invasive catheter procedure.
The process used in the trial was developed earlier by Marban when he was on the faculty at Johns Hopkins. Johns Hopkins has filed for a patent on the intellectual property and has licensed it to a company in which Marban has a financial interest. However, no funds from that company were used to support the clinical study. All funding was derived from the National Institutes of Health and Cedars-Sinai Medical Center.
This study followed another in which doctors reported using cells taken from the heart to heal the heart. That trial reported in November 2011 that cells could be used to heal the hearts of heart failure patients who were having heart bypass surgery.
And another trial is about to get underway in Europe, which will be the largest ever for stem cell therapy in heart attack patients.
The BAMI trial will inject 3,000 heart attack patients with stem cells taken from their bone marrow within five days of the heart attack.
Marban said despite the heart´s ability to re-grow heart muscle with the help of heart stem cells, they found no increase in a significant measure of the heart´s ability to pump — the left ventricle ejection fraction: the percentage of blood pumped out of the left ventricle.
Professor Anthony Mathur, a coordinating researcher for the upcoming BAMI trial, said that even if the Marban trial found an increase in ejection fraction then it would be the source of much debate. As it was a proof-of-concept study, with a small group of patients, “proving it is safe and feasible is all you can ask.”
“The findings would be very interesting, but obviously they need further clarification and evidence,” he told BBC News.
“It´s the first time these scientists´ potentially exciting work has been carried out in humans, and the results are very encouraging,” Professor Jeremy Pearson, associate medical director at the British Heart Foundation, told BBC News.
“These cells have been proven to form heart muscle in a petri dish but now they seem to be doing the same thing when injected back into the heart as part of an apparently safe procedure,” he added. “It´s early days, and this research will certainly need following up, but it could be great news for heart attack patients who face the debilitating symptoms of heart failure.”
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