Epicardial Origin of Resident Mesenchymal Stem Cells in the Adult Mammalian Heart

Abstract

The discovery of stem and progenitor cells in the adult mammalian heart has added a vital dimension to the field of cardiac regeneration. Cardiac-resident stem cells are likely sequestered as reserve cells within myocardial niches during the course of embryonic cardiogenesis, although they may also be recruited from external sources, such as bone marrow. As we begin to understand the nature of cardiac-resident stem and progenitor cells using a variety of approaches, it is evident that they possess an identity embedded within their gene regulatory networks that favours cardiovascular lineage potential. In addition to contributing lineage descendants, cardiac stem cells may also be stress sensors, offering trophic cues to other cell types, including cardiomyocytes and vasculature cells, and likely other stem cells and immune cells, during adaptation and repair. This presents numerous possibilities for endogenous cardiac stem and progenitor cells to be used in cell therapies

Atrial natriuretic peptide regulates adipose tissue accumulation in adult atria

“…3G), and expressed the nuclear marker TCF21 attesting their epicardial origin ( Fig. 3H) (20). These tdT + cells underwent EMT spontaneously, acquiring a mesenchymal morphology as observed at day 3 ( Fig.…”

“…Here we showed that the atrial epicardium is a source of adipocytes that can contribute to the accumulation of EAT in adult atria and that myocardial ANP is a trigger of this process. The capacity of epicardial cells to undergo EMT, to migrate, and to differentiate into smooth muscle cells or myofibroblasts is well established (7,9,20,39), but their adipogenic potential in adults has remained controversial (9). In the present study we found that human and mouse adult EPDCs show a strong potential to differentiate into adipocytes in vitro.…”

Developmental origin and lineage plasticity of endogenous cardiac stem cells

“…Developmental fate cCFU-F and the cardiac PDGFRα + stromal cell fraction may share properties with the epicardium and other mesothelia that give rise to stromal and smooth muscle lineages during development (Asli et al, 2014;Rinkevich et al, 2012). In the adult heart, cCFU-F have been proposed to give rise to the diverse variety of stromal cells as well as perivascular cells, adipocytes, myofibroblasts, coronary endothelial cells and (controversially) cardiomyocytes in homeostasis and disease (Asli et al, 2014).…”

“…During development, it undergoes EMT to give rise to epicardiumderived cells, which form smooth muscle cells and probably some endothelial cells of the nascent coronary vascular tree as well as interstitial stromal cells and cCFU-F. The ability of the epicardium to form significant numbers of cardiomyocytes during development remains contentious (Asli et al, 2014), although it is essential for promoting cardiomyocyte proliferation via a paracrine effect (PerezPomares and de la Pompa, 2011). Early studies showed that the adult epicardium is highly reactive to injury and is involved in immune surveillance (Gittenberger-de Groot et al, 2010;Yung and Chan, 2009).…”

“…In the adult heart, cCFU-F have been proposed to give rise to the diverse variety of stromal cells as well as perivascular cells, adipocytes, myofibroblasts, coronary endothelial cells and (controversially) cardiomyocytes in homeostasis and disease (Asli et al, 2014). Two CRE lineagetracing studies that may shed light on the fate of cCFU-F in vivo have been performed.…”