AimsWe previously showed that the protective effects of endothelial progenitor cells (EP
Cs)‐released exosomes (EP
C‐EXs) on endothelium in diabetes. However, whether EP
C‐EXs are protective in diabetic ischemic stroke is unknown. Here, we investigated the effects of EP
C‐EXs on diabetic stroke mice and tested whether miR‐126 enriched EP
C‐EXs (EP
C‐EXs
miR126) have enhanced efficacy.
MethodsThe db/db mice subjected to ischemic stroke were intravenously administrated with EP
C‐EXs 2 hours after ischemic stroke. The infarct volume, cerebral microvascular density (MVD), cerebral blood flow (
CBF), neurological function, angiogenesis and neurogenesis, and levels of cleaved caspase‐3, miR‐126, and VEGFR2 were measured on day 2 and 14.
ResultsWe found that (a) injected EP
C‐EXs merged with brain endothelial cells, neurons, astrocytes, and microglia in the peri‐infarct area; (b) EP
C‐EXs
miR126 were more effective than EP
C‐EXs in decreasing infarct size and increasing
CBF and MVD, and in promoting angiogenesis and neurogenesis as well as neurological functional recovery; (c) These effects were accompanied with downregulated cleaved caspase‐3 on day 2 and vascular endothelial growth factor receptor 2 (VEGFR2) upregulation till day 14.
ConclusionOur results indicate that enrichment of miR126 enhanced the therapeutic efficacy of EP
C‐EXs on diabetic ischemic stroke by attenuating acute injury and promoting neurological function recovery.
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