The Elusive Progenitor Cell in Cardiac Regeneration: Slip Slidin' Away

The adult human heart is unable to regenerate after various forms of injury, suggesting that this organ lacks a biologically meaningful endogenous stem cell pool. However, injecting the infarcted area of the adult mammalian heart with exogenously prepared progenitor cells of various types has been reported to create new myocardium by the direct conversion of these progenitor cells into cardiomyocytes. These reports remain controversial because follow-up studies from independent laboratories failed to observe such an effect. Also, the exact nature of various putative myocyte-producing progenitor cells remains elusive and undefined across laboratories. By comparison, the field has gradually worked toward a consensus viewpoint that proposes that the adult mammalian myocardium can undergo a low level of new cardiomyocyte renewal of ≈1% per year, which is primarily because of proliferation of existing cardiomyocytes but not from the differentiation of putative progenitor cells. This review will weigh the emerging evidence, suggesting that the adult mammalian heart lacks a definable myocyte-generating progenitor cell of biological significance.