Sevoflurane preconditioning promotes activation of resident CSCs by transplanted BMSCs via miR-210 in a rat model for myocardial infarction
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Ti Wen1, Li Wang2, Xue-Jun Sun3, Xi Zhao4, Guang-Wei Zhang4 and Jesse Li-Ling5
1Department of Oncology, The First Hospital of China Medical University, Shenyang, 110001, China
2Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
3Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, China
4Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, 110001, China
5Institute of Genetic Medicine, School of Life Science, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China
Guang-Wei Zhang, email: email@example.com
Keywords: myocardial infarction; stem cell transplantation; miR-210; regeneration; ventricular function
Received: July 29, 2017 Accepted: November 14, 2017 Published: December 09, 2017
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 SFpreBMSCs group compared with BMSCs group (P < 0.05). 4 weeks later, SFpreBMSCs 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 SFpreBMSCs 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 (SFpreBMSCs 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.
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