Cardiac microvascular functions improved by MSC-derived exosomes attenuate cardiac fibrosis after ischemia-reperfusion via PDGFR-β modulation.

Microvascular dysfunction caused by cardiac ischemia-reperfusion (I/R) leads to multiple severe cardiac adverse events, such as heart failure and ventricular modeling, which plays a critical role in outcomes. Though marrow mesenchymal stem cell (MSC) therapy has been proven effective for attenuating I/R injury, the limitations of clinical feasibility cannot be ignored. Since exosomes are recognized as the main vehicles for MSCs paracrine effects, we assumed that MSC-derived exosomes could prevent microvascular dysfunction and further protect cardiac function. By establishing a rat cardiac I/R model in vivo and a cardiac microvascular endothelial cells (CMECs) hypoxia-reperfusion (H/R) model in vitro, we demonstrated that MSC-derived exosomes enhanced microvascular regeneration under stress, inhibited fibrosis development, and eventually improved cardiac function through platelet-derived growth factor receptor-β (PDGFR-β) modulation. Furthermore, we found that MSC-derived exosomes possessed better therapeutic effects than MSCs themselves.