Cardiosphere-Derived Cell Exosomes Enhance Macrophage Efferocytosis To Reduce Infarct Size Following Ischemia/Reperfusion Injury

Introduction: Cardiosphere-derived cells (CDCs) and CDC exosomes (CDCexo) are cardioprotective against ischemia/reperfusion (I/R) injury if delivered within 20-30 mins of reperfusion (Kanazawa et al, Circ HF 2015; de Couto et al, JCI 2015; de Couto et al, Circ 2017; Lefer u0026 Marban, Circ 2017). The effects of CDC-mediated protection have been attributed to distinctive polarization of macrophages (Mφ). Enhanced phagocytic capacity is the key phenotypic feature of CDCexo-primed Mφ. Here we show that CDCexo scavenge cellular debris from dying cells (i.e., efferocytosis) to attenuate infarct expansion following I/R. Methods u0026 Results: To test whether CDCexo enhance Mφ efferocytosis in vitro, bone marrow-derived Mφ were primed toward M1 (LPS u0026 IFNγ), M2 (IL-4 u0026 IL-13), or exposed overnight to fibroblast exosomes (MFBexo) or CDCexo (MCDCexo). The following day, neonatal rat ventricular myocytes were stained with DiI, UV-irradiated to induce apoptosis, and then placed in co-culture with primed Mφ. One hour later,...