PDGFRα signaling in cardiac stem and stromal cells modulates quiescence, metabolism and self-renewal, and promotes anatomical and functional repair

The interstitial and perivascular spaces of the heart contain stem-like cells including cardiac colony forming units - fibroblast (cCFU-F), a sub-fraction of SCA1+PDGFRα+CD31- (S+P+) immature stromal cells with the qualities of mesenchymal stem cells, that we have characterized previously. Here we explore the role of platelet-derived growth factor receptor α (PDGFRα) in cCFU-F and S+P+ cell niche regulation in homeostasis and repair. PDGFRα signaling modulated quiescence, metabolic state, mitogenic propensity and colony formation, as well as the rate and stability of self-renewal. Exogenously administered PDGF-AB ligand had anti-aging effects on cCFU-F, akin to those seen in heterochronic parabiotic mice. Post-myocardial infarction (MI), exogenous PDGF-AB stimulated S+P+ cell proliferation and conversion to myofibroblasts through a metabolic priming effect, yet significantly enhanced anatomical and functional repair via multiple cellular processes. Our study provides a rationale for a novel therapeutic approach to cardiac injury involving stimulating endogenous repair mechanisms via activation of cardiac stem and stromal cells.