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Study Urges Caution in Stem Cell Trials for Heart Attack Patients

Controversial treatment doesn’t generate cardiomyocytes, authors say

A new study in Nature challenges research data that form the scientific basis of clinical trials in which heart attack patients are injected with stem cells to try and regenerate damaged heart tissue.

Researchers at Cincinnati Children’s Hospital Medical Center and the Howard Hughes Medical Institute reported May 7 that cardiac stem cells used in ongoing clinical trials — which express a protein marker called c-kit — do not regenerate contractile heart-muscle cells at high enough rates to justify their use for treatment.

The study found new evidence in what has become a contentious debate in the field of cardiac regeneration, according to principal investigator Jeffery Molkentin, PhD.

“Our data suggest that any potential benefit from injecting c-kit–positive cells into the hearts of patients is not because they generate new contractile cells, called cardiomyocytes,” Molkentin said. “Caution is warranted in further clinical testing of this method until the mechanisms in play are better defined or we are able to dramatically enhance the potential of these cells to generate cardiomyocytes.”

Numerous heart attack patients have been treated with c-kit–positive stem cells, which are removed from healthy regions of a damaged heart and are then processed in a laboratory, Molkentin explained. After processing, the cells are injected back into patients’ hearts. The experimental treatment is based largely on data from preclinical studies in rats and mice, which suggested that c-kit–positive stem cells completely regenerate myocardial cells and heart muscle. Thousands of patients have also undergone a similar procedure, but with bone-marrow stem cells.

According to Molkentin and his colleagues, the previous preclinical studies in rodents do not reflect what actually occurs in the heart after injury, where the internal regenerative capacity is almost nonexistent. Molkentin also said that combined data from multiple clinical trials testing this type of treatment showed that most patients experienced only a 3% to 5% improvement in the left ventricular ejection fraction — a measurement of how forcefully the heart pumps blood. Data in the new Nature study suggest that this small benefit may come from the ability of c-kit–positive stem cells in the heart to cause the growth of capillaries, which improves circulation within the organ, and not from the creation of new cardiomyocytes.

“What we show in our study is that c-kit–positive stem cells from the heart like to make endothelial cells that form capillaries. But in their natural environment in the heart, these c-kit–positive cells do not like to make cardiomyocytes,” Molkentin said. “They will produce cardiomyocytes, but at rates so low — roughly one in every 3,000 cells — that it becomes meaningless.”

Source: Cincinnati Children’s Hospital; May 7, 2014.

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