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BackgroundExosomes derived from mesenchymal stem cells (MSCs) were proved to boost cell proliferation and angiogenic potency. We explored whether cardiac stem cells (CSCs) preconditioned with MSC exosomes could survive and function better in a myocardial infarction model. Methods and ResultsDiI‐labeled exosomes were internalized with CSCs. They stimulated proliferation, migration, and angiotube formation of CSCs in a dose‐dependent manner. In a rat myocardial infarction model, MSC exosome–preconditioned CSCs had significantly better survival, enhanced capillary density, reduced cardiac fibrosis, and restored long‐term cardiac function. MicroRNA profiling analysis revealed that a set of microRNAs were significantly changed in CSCs after MSC exosome treatment. ConclusionsPretreatment of CSCs with MSC exosomes provided a promising strategy to improve survival and angiogenic potency of CSCs.