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Editorial
November 27, 2018

A Time to Press Reset and Regenerate Cardiac Stem Cell Biology

Author Affiliations
  • 1Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
  • 2Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
  • 3Institute for Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
  • 4The Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
JAMA Cardiol. 2019;4(2):95-96. doi:10.1001/jamacardio.2018.4435

In 2001, a research team published 2 high-profile reports1,2 suggesting that bone marrow could regenerate the heart and new myocytes are formed in the human heart at a substantial and surprising rate. The articles upended existing dogma and contradicted years of rigorous analysis. Researchers struggled to reproduce the findings with limited success, and Nature took the unusual step of publishing 3 separate negative studies in 2003 and 2004 suggesting that bone marrow could not regenerate myocardium.3-5 Other researchers found that new myocardial cells in the adult heart are formed only rarely, if at all.6 Nevertheless, a cadre of researchers continued to publish work supporting the possible existence of bone marrow–derived cardiac stem cells and received millions of dollars from federal agencies and foundations for their ongoing research. Unchecked optimism by many in the cardiology community led to rapidly initiated clinical trials despite the controversy, and over the next decade, thousands of patients received cardiac infusions of putative stem cells both within and outside of clinical trials sponsored by the National Institutes of Health (NIH), costing taxpayers additional millions of dollars. When it became clear that bone marrow does not contain cardiac stem cells, researchers reported the existence of a different, resident cardiac stem cell within the heart itself that could regenerate the myocardium.4 When subsequent studies failed to show myogenic differentiation of these putative resident stem cells in vivo, yet another theory was generated to defend the purported benefit of injecting these nonstem cells into the heart; perhaps they were secreting a beneficial paracrine factor that caused the heart to regenerate, although the nature of such a factor was elusive and the benefits transitory at best.

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