Muscle cells, transplanted from elsewhere in the body, could one day be used to help heal a patient’s damaged heart, according to new research led by Francis Pagani, M.D., Ph.D., an associate professor of surgery in the U-M Medical School and director of the Heart Transplant Program.

Frank Pagani Photo: Gregory Fox

In the phase I study, several U-M cardiac patients who were waiting for heart transplants had cells from the quadriceps muscle in their thighs injected into their hearts. After the transplant, their old, damaged hearts were examined for signs of new cell growth. Scientists found that the injected cells not only survived in their new environment, they also began forming muscle fibers. Researchers noticed an increase in the formation of small blood vessels near the injection site. None of the patients developed immune reactions to the transplants. Results were announced at the American Heart Association meeting in November 2002.

The multi-part study, sponsored by Diacrin, Inc., of Charlestown, Massachusetts, involved patients at several medical institutions. U-M Health System patients received injections of skeletal muscle cells during implantation of a heart-assist device called an LVAD, which boosts the failing heart’s pumping power and helps patients survive until a new heart is available for transplant. Satellite muscle cells, which occur naturally in skeletal muscle and help repair damage, were injected into the wall of the heart’s pumping chamber during the LVAD procedure.

After the heart transplant, the old heart was removed and sent to Diacrin for testing. “We found direct evidence of skeletal muscle cell survival and differentiation into mature muscle fibers, measured using antibodies that specifically target skeletal muscle cells,” says Pagani, who directs the Heart Transplant Program in the U-M Cardiovascular Center. “Because cardiac muscle and skeletal muscle are two distinct types of tissue, the antibody test shows conclusively that the transplanted cells survived.”

In addition to the encouraging finding that the injected cells “grafted” into their new environment, the results showed that the patients’ hearts did not reject the transplanted cells. No evidence of an immune reaction was found in either grafted or non-grafted areas.

“Because the skeletal muscle cells are from the patient’s body, we don’t expect the kind of immune reaction and rejection we often see in transplants of whole hearts from donors,” says Pagani. Pagani stressed that these early results, while encouraging, are merely the first steps in evaluating the potential of using muscle cell transplants to heal damaged hearts.

In addition to Pagani, the research team included Keith Aaronson, M.D., U-M assistant professor of internal medicine and medical director of the U-M Heart Transplant Program, research coordinator Sue Wright, R.N., and several collaborators from Massachusetts General Hospital. Physicians and patients from the Arizona Heart Institute and Temple University were also involved in the study.

—KG

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U-M Cardiovascular Center