The cardiac stem cell niche during aging

Abstract

Abstract The adult mammalian heart has a long-standing reputation as a post-mitotic organ, largely incapable of self-regeneration. However, in the past 20 years this reputation has been called into question. Reasons for this include definitive evidence of cardiomyocyte turnover over the mammalian lifespan and reports of cardiac resident stem cell populations. During embryonic development, the heart forms from three distinct progenitor populations; the cardiogenic mesoderm, the proepicardium and a sub-population of migrating neural crest cells. Utilizing elegant lineage tracing studies and transgenic animal models, researchers have mapped the contributions of these progenitor populations to the mature heart and identified persisting populations of adult progenitors located in the sub-epicardium and throughout the myocardial interstitium. Several discrete cardiac progenitor subpopulations have been characterized based on their clonogenic properties and cell surface marker signatures, including cKit + progenitors, Sca-1 + progenitors, cardiospheres and cardiac colony forming unit-fibroblasts (CFU-Fs). Upon activation, cardiac progenitors are capable of differentiating into cardiac fibroblasts, endothelium and smooth muscle, although their cardiomyogenic potential is still a topic of debate. In this chapter, we discuss the developmental origins, locations and features of cardiac stem cell niches in the adult heart and review current evidence for the role of resident cardiac stem and progenitor cells in cardiac repair and cardiomyocyte replacement after myocardial infarction. We also highlight the important roles of non-myocytes and the extracellular matrix (ECM) in the maintenance of cardiac stem cell niches, structural integrity and repair, and the development of fibrosis in the aging heart.