Cardiac regeneration using stem cells may heal hearts even years after heart attacks

Left ventricular function and exercise capacity increased, while the area of heart muscle damage shrank, in 18 patients given infusions of their own bone marrow stem cells up to eight years after a heart attack, according to a new study in the Nov. 1, 2005, issue of the Journal of the American College of Cardiology.

"This new therapy is able to treat until now irreversible heart complaints and function disturbances in patients with chronic coronary artery disease after myocardial infarction, even many years after heart attack. Therefore there is hope for this large amount of patients with previous myocardial infarction and non-treatable complaints," said Bodo E. Strauer, M.D. from the Heinrich-Heine-University in Dusseldorf, Germany.

If further trials produce similar results, cardiac regeneration using stem cells could help to not only reverse some heart attack damage, reduce symptoms and improve the daily functioning of patients; it might also reduce the risk of heart failure, Dr. Strauer said.

Current heart attack interventions attempt to restore blood flow to the heart muscle as soon as possible, in order to limit the amount of permanent scarring. However, neither clotbusting drugs nor angioplasty can restore heart tissue that has already been damaged. Earlier studies demonstrated healing of heart muscle and improved heart function following injections of stem cells directly into the heart muscle or infusions of stem cells into key heart arteries soon after a heart attack.

This study is the first to report the results of stem cell infusions into the arteries of patients many months or years after a heart attack. The researchers harvested bone marrow from the hip bones of the patients, so there was no threat of transplant rejection. After processing, stem cells from the marrow were infused through a catheter into the coronary artery where the patient's heart attack occurred.

"The main results were at least threefold: an improvement in global left ventricular function by 15 percent, infarction wall movement velocity rose 57 percent, and there was a significant reduction of infarct size by 30 percent. Concerning all those parameters, no significant changes were seen in a representative control group. Moreover, after bone marrow cell transplantation, an improvement of maximum oxygen uptake by 11 percent and of 18F-fluor-desoxy-glucose uptake by 15 percent, which represents myocardial metabolism and viability, into infarct tissue was observed," Dr. Strauer said.

"The stem cell therapy demonstrates that restoration is possible, clinically feasible and associated with an improvement of the performance of the heart by approximately 20 to 30 percent. This therapy is safe, similar to an 'own blood injection or transfusion,' and has no side effects. It needs only bone marrow puncture and cell aspiration with subsequent stem cell preparation," he said.

Although this study did not look at how stem cells may heal heart attack damage, other studies have shown that the bone marrow cells can differentiate to become heart muscle cells or cells that line blood vessels. In addition, chemical signals from the bone marrow stem cells may stimulate the growth of surviving heart muscle tissue, prompt stem cells already within the heart into action, or perhaps fuse with and revitalize damaged heart muscle cells.

"It should be noted that until now only 18 patients have been transplanted and were compared to a representative control group. This means that we need to concentrate on a larger, prospective randomized controlled trial in order to strengthen the statistical power of the positive results," Dr. Strauer said.

Larger trials are already underway. Meanwhile, researchers continue to refine the techniques for harvesting, processing and delivering stem cells into the damaged muscle tissue of heart attack patients.

Piero Anversa, M.D., from the New York Medical College in Valhalla, New York, who was not connected with this study, called the results "extremely interesting."

"The data are strongly suggestive. The data are very interesting. However, let's do a double-blind clinical trial and then we'll know for sure where we stand at this stage."

Dr. Anversa said the field of cardiac regeneration is moving fast, and he expects that ultimately it will change heart attack treatment.

Reida El Oakley, F.R.C.S., M.D., from King Fahd Medical City in Riyadh, Saudi Arabia and the National University of Singapore, who also was not connected with this study, said that in addition to confirming the safety of this type of stem cell infusion, the results help add evidence that the treatment may provide meaningful benefits to patients.

"Strauer et al. provide this indirect evidence of muscle regeneration using a simple technique to isolate mononuclear cells from the patient's own bone marrow, then transplanting these cells through the coronary artery feeding the damaged section of the heart muscle," Dr. El Oakley said. "The success of this approach will grow with time, yet more research is required to identify the ideal route of implantation, and the type of cell transplantation that is most efficient for regenerating damaged myocardium."

Roberto Bolli, M.D., F.A.C.C., from the University of Louisville in Louisville, Kentucky, who co-authored an editorial appearing in the journal, wrote that a "veritable revolution" is underway to overthrow the belief that heart muscle was incapable of regeneration. He said that previous studies showed benefits from injecting stem cells directly into damaged heart muscle or performing intracoronary infusions of stem cell into affected coronary arteries soon after a heart attack.

"The importance of the present study is that it shows that intracoronary delivery of bone marrow cells improves function and flow in patients with old myocardial infarction. This widens dramatically the applicability of stem cell therapies," Dr. Bolli said. "I believe that clinical applicability of stem cells will become a reality in one to two years."

Dr. Bolli pointed out that since the Strauer et al. study was not randomized nor double-blinded, and involved only 18 patients, it does not provide conclusive proof that the technique is effective. However, he noted that the results of large randomized, double-blinded clinical trials are expected soon.