biostudies-literatureJung JHAmerican Heart AssociationNHLBI NIH HHSNational Heart, Lung, and Blood InstituteNational Institutes of HealthNIH HHS19https://www.ebi.ac.uk/biostudies/studies/S-EPMC8601755biostudies-literatureUnknown116(1)Endogenous capability of the post-mitotic human heart holds great promise to restore the injured myocardium. Recent evidence indicates that the extracellular vesicles (EVs) regulate cardiac homeostasis and regeneration. Here, we investigated the molecular mechanism of EVs for self-repair. We isolated EVs from human iPSC-derived cardiomyocytes (iCMs), which were exposed to hypoxic (hEVs) and normoxic conditions (nEVs), and examined their roles in in vitro and in vivo models of cardiac injury. hEV treatment significantly improved the viability of hypoxic iCMs in vitro and cardiac function of severely injured murine myocardium in vivo. Microarray analysis of the EVs revealed significantly enriched expression of the miR-106a-363 cluster (miR cluster) in hEVs vs. nEVs. This miR cluster preserveBasic research in cardiologymiR-106a-363 cluster in extracellular vesicles promotes endogenous myocardial repair via Notch3 pathway in ischemic heart injury.PMC860175519CSLOI34700047-lUM1 HL11345618POST34080005K24 HL130553UM1 HL087394Jeon YJO'brien CGWahlquist CJung JHSantoso MRAppel EAMercola MIkeda Gvon Bornstadt DYang PCYu ACRed-Horse KTada YRhee SWoo JfalsemiR-106a-363 cluster in extracellular vesicles promotes endogenous myocardial repair via Notch3 pathway in ischemic heart injury.Endogenous capability of the post-mitotic human heart holds great promise to restore the injured myocardium. Recent evidence indicates that the extracellular vesicles (EVs) regulate cardiac homeostasis and regeneration. Here, we investigated the molecular mechanism of EVs for self-repair. We isolated EVs from human iPSC-derived cardiomyocytes (iCMs), which were exposed to hypoxic (hEVs) and normoxic conditions (nEVs), and examined their roles in in vitro and in vivo models of cardiac injury. hEV treatment significantly improved the viability of hypoxic iCMs in vitro and cardiac function of severely injured murine myocardium in vivo. Microarray analysis of the EVs revealed significantly enriched expression of the miR-106a-363 cluster (miR cluster) in hEVs vs. nEVs. This miR cluster preserve2021-01-01T00:00:00Z2021 Mar2025-04-04T19:58:03.81Z2025-04-04T19:58:03.81ZS-EPMC86017553374227610.1007/s00395-021-00858-8