Endogenous Regeneration of the Mammalian Heart

  • Konstantinos Malliaras


The adult mammalian heart, once viewed as a postmitotic organ, is now considered a regenerative organ. The human heart’s regenerative capacity peaks during childhood and decreases exponentially with age. While this innate regenerative capacity is limited, the study of the cellular sources of innate regeneration and the molecular pathways that govern it is certainly merited; elucidation of the endogenous regenerative mechanisms of the mammalian heart could enable their therapeutic exploitation. With regard to the cellular sources of myocyte turnover, cardiomyocyte proliferation has emerged as the dominant mechanism of myocyte replenishment in the injured neonatal heart and in the healthy adult heart during normal aging. Following myocardial injury of the adult heart, myocyte proliferation increases. Endogenous progenitors may also contribute to cardiomyogenesis in the injured mammalian heart, although this is not universally accepted and remains a subject of intense debate. Regarding therapeutic ways to stimulate cardiac regeneration, several strategies have yielded promising results in animal testing, including genetic manipulation of the cell cycle, regulation of miRNA expression, modulation of the Hippo and neuregulin/ERBB signaling pathways, administration of mitogenic factors, exposure to hypoxia, exercise, cell therapy, and mechanical unloading with left ventricular assist devices. Clinical translation of such therapeutic strategies is of utmost importance, as safe and reliable exogenous stimulation of endogenous regenerative processes will undoubtedly enable development of more effective treatments for a wide spectrum of cardiac diseases.


Cardiac regeneration Myocyte turnover Cardiomyocyte proliferation Cardiac stem cells Cyclin Neuregulin Periostin Hippo pathway 


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Konstantinos Malliaras
    • 1
  1. 1.Department of CardiologyLaikon HospitalAthensGreece

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