Revealing Pathways of Cardiac Regeneration

ajor cardiac injuries like a large myocardial infarction lead to systolic heart failure because of loss of cardiomyocytes. Unlike during embryonic development, 1 adult mammalian cardiomyocytes have limited ability to proliferate and replenish the adult mammalian heart. Although there was once excitement over possible adult cardiac stem cells residing in the mammalian myocardium, it now seems that there are insufficient cardiac progenitor cells in the heart 2 to generate any meaningful regeneration. More recently, it was discovered that the heart's regenerative ability is preserved in the first hours after birth in mice 3 and rats. 4 Indeed, cardiac regeneration may be recapitulated in vitro using immature human heart organoids, 5 indicating an innate capacity of some cardiomyocytes for regeneration. These and other recent discoveries have advanced our understanding of how the mammalian heart can regenerate under certain circumstances, potentially setting the stage for us to appreciate why adult human hearts fail to regenerate.