Cardiac stem cells as a source of myocardial regeneration

Abstract According to traditional concepts, cardiac muscle tissue is considered incapable of regeneration at the cellular level because it does not contain cambial elements that could replace lost cardiomyocytes. As a result, various myocardial injuries result in closure of the defect with a connective tissue scar, followed by the development of heart failure. However, the results of some studies over the past two decades indicate the presence of a heterogeneous population of stem and progenitor cells in the heart. Available data indicate that these cells can facilitate the restoration of pathologically altered myocardium by differentiating into its cellular components (endothelial cells, vascular smooth muscle cells, and possibly cardiomyocytes) or by exerting a paracrine regulatory influence on damaged tissue. The discovery of cardiac stem cells has opened new perspectives in the treatment of various heart diseases. At the same time, data on their regenerative potential, particularly regarding their ability to differentiate into cardiomyocytes, are controversial, and the therapeutic efficacy of their transplantation in patients remains questionable. In particular, new methods of genetic lineage-tracing have revealed that the c-kit and Sca-1 markers, traditionally used for sorting cardiac stem cells, predominantly identify endothelial lineage cells lacking cardiomyogenic potential. This review examines the phenotypic and functional characteristics of different cardiac stem cell populations, their localization in the heart, age-related dynamics, changes in pathological conditions, as well as mechanisms of their pro-regenerative effects, and potential clinical applications.