Stem cells repair damaged heart muscle in preliminary study

Treatment shown to reduce scar tissue, improve patients' quality of life

Stem cells can effectively repair damaged heart muscle in patients with chronic heart failure, reducing scar tissue and improving their quality of life, according to a preliminary study by researchers at Johns Hopkins and the University of Miami.

In a study of 31 patients, results indicated that stem cell treatment was safe and beneficial, regardless of whether the cells came from the patient's own bone marrow or from a healthy volunteer

An article describing the study was published online by the Journal of the American Medical Association on Nov. 6. Results were presented that same day at the American Heart Association Scientific Sessions in Los Angeles.

According to the researchers, from the Johns Hopkins University School of Medicine and the University of Miami Miller School of Medicine, this is the first study to compare autologous stem cells, which are derived from the patients' own bone marrow, to allogeneic stem cells, taken from the marrow of healthy volunteers, in patients with heart disease. The advantage of using allogeneic cells is the potential for developing an off-the-shelf therapy that could be delivered in a more timely manner, rather than requiring a bone marrow biopsy from heart failure patients and waiting for the cells to be processed. Also, stem cells from the patients themselves may not be as robust.

All of the study patients had chronic heart failure caused by a prior heart attack that blocked blood flow to the heart and damaged heart muscle. The condition affects about 70 percent of the six million people in the United States who suffer from heart failure.

"The primary focus of our study was to determine the safety of the therapy, specifically within 30 days of the treatment," said Gary Gerstenblith, professor of medicine at the Johns Hopkins University School of Medicine and co-author of the study. "We found that the treatment was safe and also that many of the patients experienced significant improvement, whether they had received the allogeneic or the autologous stem cells."

Patients in the study were randomly selected to have either their own stem cells or donated cells injected directly into their heart muscle. They were monitored for treatment-associated complications, including death, heart attack, stroke, hospitalization for worsening heart failure, and dangerous heart arrhythmias. All of the patients were still alive 12 months after the treatment.

The researchers were especially interested in learning whether the patient's immune system would recognize the donated stem cells as foreign and mount an immune response to reject the cells. Only 3.7 percent of the patients receiving the donated cells had such a response. The cells were injected into the heart muscle just once during a cardiac catheterization procedure.

The particular cells used for the therapy, mesenchymal stem cells, are less likely to stimulate an immune response and rejection than most other stem cells. They have the ability to repair muscular tissues and to reduce inflammation.

Patients in the allogeneic and autologous groups were further divided according to the doses of the stem cells they received. Three different doses were tested: 20 million cells, 100 million cells, and 200 million cells.

"We generally think the more the better, but in fact, the lowest dose of 20 million cells appeared to be the most effective at improving the heart's pumping ability as well as reducing the extent of scar tissue," said Peter Johnston, assistant professor of medicine at Johns Hopkins and co-author of the study.

Both groups experienced a reduction in scar tissue, Johnston said, which is important because scar tissue can impede the heart's normal functioning and increase the risk of heart rhythm abnormalities. Also, the size of many patients' hearts became more normal over the course of the study. As heart failure worsens, the heart becomes enlarged and is less able to pump effectively.

After the stem cell therapy, many patients were able to walk farther on a six-minute walking test and reported an improved quality of life on a questionnaire administered multiple times during the 12-month study period.

"In many cases we observed clinically significant improvement," said Joshua Hare, director of the Interdisciplinary Stem Cell Institute at the University of Miami Miller School of Medicine and the lead author of the study. "Even in patients who had heart attacks several decades before treatment, both donor and recipient stem cells reduced the amount of scarring substantially."

Added Johnston: "The results are very encouraging because our current therapies are aimed at decreasing the heart's workload and making patients feel better, but none can truly repair the heart or reverse the damage caused by heart attacks."

The next steps, according to Gerstenblith, are to conduct studies comparing the therapy with a placebo and learn whether repeated doses result in better outcomes, as well as to study the safety and effectiveness of stem cell therapy in patients with other causes of heart failure.

"The findings of our study strongly support ongoing development of allogeneic stem cell therapy for the increasing number of patients with advanced heart failure," Gerstenblith said.