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10.3389/fnmol.2017.00080

http://scihub22266oqcxt.onion/10.3389/fnmol.2017.00080
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pmid28424584      Front+Mol+Neurosci 2017 ; 10 (ä): 80
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  • Hif-1alpha Overexpression Improves Transplanted Bone Mesenchymal Stem Cells Survival in Rat MCAO Stroke Model #MMPMID28424584
  • Lv B; Li F; Han J; Fang J; Xu L; Sun C; Hua T; Zhang Z; Feng Z; Jiang X
  • Front Mol Neurosci 2017[]; 10 (ä): 80 PMID28424584show ga
  • Bone mesenchymal stem cells (BMSCs) death after transplantation is a serious obstacle impacting on the outcome of cell therapy for cerebral infarction. This study was aimed to investigate whether modification of BMSCs with hypoxia-inducible factor 1alpha (Hif-1alpha) could enhance the survival of the implanted BMSCs. BMSCs were isolated from Wistar rats, and were infected with Hif-1alpha-GFP lentiviral vector or Hif-1alpha siRNA. The modified BMSCs were exposed to oxygen-glucose deprivation (OGD) condition, cellular viability and apoptosis were then assessed. An inhibitor of AMPK (compound C) was used to detect whether AMPK and mTOR were implicated in the functions of Hif-1alpha on BMSCs survival. Besides, ultrastructure of BMSCs was observed and the expression of autophagy markers was measured. The modified BMSCs were transplanted into middle cerebral artery occlusion (MCAO) model of rats, and the cerebral infarction volume and neurological function was assessed. The results indicated that Hif-1alpha overexpression protected OGD induced injury by promoting cellular viability and inhibiting apoptosis. AMPK was activated while mTOR was inactivated by Hif-1alpha overexpression, and that might be through which Hif-1alpha functioned BMSCs survival. Hif-1alpha overexpression promoted autophagy; more important, compound C abolished the induction of Hif-1alpha on autophagy. Transplantation of the overexpressed Hif-1alpha of BMSCs into the MCAO rats reduced brain infarct volume and improved neurobehavioral outcome; besides, it inhibited pro-inflammatory cytokines generation while promoted neurotrophin secretion. In conclusion, Hif-1alpha might be contributed in the survival of BMSCs by regulating the activation of AMPK and mTOR, as well as by promoting autophagy.
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