Sevoflurane preconditioning promotes activation of resident CSCs by transplanted BMSCs via miR-210 in a rat model for myocardial infarction

OBJECTIVE: To assess the effect of sevoflurane preconditioning (SFpre) on bone marrow mesenchymal stem cells (BMSCs) for the treatment of acute myocardial infarction. RESULTS: 24 hours after the transplantation, decreased apoptosis of implanted BMSCs and up-regulation of cytokines expression were found within the ischemic area in (SFpre)BMSCs group compared with BMSCs group (P < 0.05). 4 weeks later, (SFpre)BMSCs group showed more viable implanted BMSCs, CSC-derived cardiomyocytes, and higher vessel and myocardial density within the infarcted region and improved cardiac function, compared with control and BMSCs groups (P < 0.05). Compared with untreated BMSCs, promoted migration, inhibited apoptosis, increased cytokine secretion, and enhanced activation to CSCs were detected in (SFpre)BMSCs exposed to profound hypoxia and serum deprivation, via up-regulating miR-210 expression (P < 0.05). CONCLUSIONS: Sevoflurane preconditioning can protect BMSCs against hypoxia by activating miR-210 expression and promote their paracrine functions and effects on resident CSCs. METHODS: After the preconditioning, rat BMSCs ((SFpre)BMSCs group) were transplanted into rat AMI models, while BMSCs group received unconditioned BMSCs. Apoptosis and paracrine functions of the transplanted BMSCs, angiogenesis, resident cardiac stem cells (CSCs) derived myocardial regeneration, cardiac function and remodeling were assessed at various time points. In vitro experiments were performed to determine the expression of miR-210 in BMSCs exposed to sevoflurane and the effect of sevoflurane on BMSCs’ migration, apoptosis and secretion of cytokines under hypoxic condition, as well as cytokine-induced CSCs activation.