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Review: Stem Cell Tx for Heart Failure Not Ready Yet

— More and better studies still needed to realize promise

MedpageToday

Heterogeneity in methods for trials of stem cell therapies for heart failure are a big reason for the inconsistent results seen to date, a review article suggested.

"In the past 2 decades, researchers have achieved significant milestones toward their goal of bringing stem cell regenerative medicine to the bedside," according to , of Stanford University School of Medicine, Calif., and colleagues online in .

"First, evidence suggests the benefit of adult stem cell therapy is likely mediated by the release of cardioprotective factors that activate endogenous pathways to repair the myocardium rather than de novo cardiomyocyte regeneration. Second, safe delivery of cells has been demonstrated in both preclinical and clinical trials."

However, the latest randomized clinical trials have found a modest clinical benefit at best among patients receiving stem cell therapy, and in some cases no effect, which the authors suggested may be due to variations in trial methods, discrepancies in reporting, and excessive reliance on surrogate endpoints.

Across 29 randomized clinical trials and 7 meta-analysis, Wu's group observed major differences in the types of heart disease and patients studied since 2000. What's more, the variety in stem cells -- derived from bone marrow, adipose tissue, umbilical cord, or cardiac tissue -- as well as cell dosage and delivery route fell far short of a standardized protocol.

"Additional studies are needed to identify the optimal strategy for clinical application," the authors concluded.

They also pointed out the common use of surrogate endpoints such as left ventricular ejection fraction, infarct size, and perfusion defects to evaluate stem cell therapy. Better yet, more definitive endpoints such as death and myocardial infarction rates should be assessed, they urged.

"Most stem cell therapy [studies] have been plagued by not being precise about the kind of cells used, the appropriate end points and picking the right population of patients to include in the trial," agreed , of University at Buffalo, N.Y., when asked for comment by 51˶.

"The question is how it will help heart failure patients. Is it by promoting positive remodeling or reducing sudden cardiac death?"

"I believe that the advances will come from better understanding the biology of stem cells," Iyer said. "There is a great need to perform translational studies in large animal models of heart failure to better understand the mechanisms before we can predict success in humans."

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    Nicole Lou is a reporter for 51˶, where she covers cardiology news and other developments in medicine.

Disclosures

No conflicts of interest were declared by the authors.

Iyer declared serving as a local principal investigator for the ongoing ALLSTAR trial.

Primary Source

JAMA Cardiology

Nguyen PK, et al "Adult stem cell therapy and heart failure, 2000 to 2016: A systematic review" JAMA Cardiol 2016; DOI: 10.1001/jamacardio.2016.2225.