Bone marrow-derived mesenchymal stem cells(BMSCs)have been demonstrated ameliorating neurologic deficits after stroke.Hypoxia-inducible factor-1(HIF-1),the key regulator of cellular responses to low oxygen concentration,can activate multiple genes involving in crucial aspects for neurologic recovery.In this study,we present that rat BMSCs overexpression of HIF-1showed higher expression of HIF-1 target genes in HIF-1-BMSCs,including CXCR4,EPO,and VEGF.BMSCs-mHIF-1 also exhibited an enhanced mobility towards the ischemic area within rat brain.Neural cell apoptosis in ischemic brain shown less severe in rats transplanted with HIF-1-BMSCs.Furthermore,the number of cells expressing neural progenitor markers PAX6 and DCX were increased in BMSCs-mHIF-1-transplanted rats.These results suggest that HIF-1 in BMSCs reduces neuronal apoptosis and promotes neurogenesis after stroke in rats.
YE ZhiZhongYE WeiBiaoDENG YuBinWANG JueZHOU GuangQianZHANG XiuQuan