Epicardium-Derived Cardiac Mesenchymal Stem Cells: Expanding the Outer Limit of Heart Repair

T he epicardium is derived from the proepicardial organ, a source of multipotent progenitor cells. Epicardium contribution to the developing coronary vasculature and to cardiac interstitial cells has been established. Studies over the past several years have suggested that epicardium-derived cells can adopt cardiomyocyte and vascular smooth muscle fates and can contribute to cardiac repair when activated by injury. 1,2 Recently, Chong et al 3 have provided a detailed characterization of a population of epicardium-derived multipotent cardiac progenitor cells (cCFU-Fs). These cells, which do not arise from the bone marrow, neural crest, or myocardium, resemble mesenchymal stem cells (MSCs) and may participate in cardiac development, homeostasis, and repair. uring early cardiac development, cells derived from the proepicardial organ (a cluster of cells located dorsal and adjacent to the looped heart tube) migrate over the myocardium to form the epicardium. Subsequently, epicardiumderived progenitor cells undergo epithelial-to-mesenchymal transition, invade the underlying myocardium, and differentiate into various cardiac lineages. Signals and cellular contributions from the epicardium have been shown to be indispensable for the establishment of normal coronary vasculature and myocardial architecture. Cardiac interstitial cells arise from epicardium, and recent studies have suggested that reactivation of the epicardium after injury could contribute to scarring or myocardial repair after injury. n this context, the recent report from Chong et al 3 is particularly relevant, because they used rigorous gene expression, culture, and fate lineage analysis to characterize a population of multipotent MSC-like cells resident in the heart that they called cardiac colony-forming units-fibroblast (cCFU-Fs). These cells derive from the proepicardium, not