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Genetic modification of miR-34a enhances efficacy of transplanted human dental pulp stem cells after ischemic stroke

查看全文 作　　者：Jianfeng [1]Wang;Peibang [1]He;Qi [1]Tian;Yu [2]Luo;Yan [3]He;Chengli [1]Liu;Pian [1]Gong;Yujia [1]Guo;Qingsong [2]Ye;Mingchang [1]Li 高影响力作者 机构地区：[1]Department of Neurosurgery,Renmin Hospital of Wuhan University,Wuhan,Hubei Province,China;[2]Center of Regenerative Medicine,Renmin Hospital of Wuhan University,Wuhan,Hubei Province,China;[3]Institute of Regenerative and Translational Medicine,Tianyou Hospital,Wuhan University of Science and Technology,Wuhan,Hubei Province,China高影响力机构 出　　处：《Neural Regeneration Research》索引2023年第18卷第9期,共8页高影响力期刊 基　　金：supported by the National Natural Science Foundation of China,Nos.81971870 and 82172173 (both to ML)。 摘　　要：Human dental pulp stem cells(hDPSCs) promote recovery after ischemic stro ke;however,the therapeutic efficacy is limited by the poor survival of transplanted cells.For in vitro expe riments in the present study,we used oxygen-glucose deprivation/reoxygenation in hDPSCs to mimic cell damage induced by ischemia/reperfusion.We found that miRNA-34a-5p(miR-34a) was elevated under oxygen-glucose deprivation/reoxygenation conditions in hDPSCs.Inhibition of miR-34a facilitated the prolife ration and antioxidant capacity and reduced the apoptosis of hDPSCs.Moreove r,dual-luciferase reporter gene assay showed WNT1and SIRT1 as the targets of miR-34a.In miR-34a knockdown cell lines,WNT1 suppression reduced cell prolife ration,and SIRT1 suppression decreased the antioxidant capacity.Togethe r,these results indicated that miR-34a regulates cell prolife ration and antioxidant stress via targeting WNT1 and SIRT1,respectively.For in vivo expe riments,we injected genetically modified hDPSCs(anti34a-hDPSCs) into the brains of mice.We found that anti34a-hDPSCs significantly inhibited apoptosis,reduced cerebral edema and cerebral infarct volume,and improved motor function in mice.This study provides new insights into the molecular mechanism of the cell prolife ration and antioxidant capacity of hDPSCs,and suggests a potential gene that can be targeted to improve the survival rate and efficacy of transplanted hDPSCs in brain after ischemic stroke. 关 键 词：antioxidant capacity HO-1 human dental pulp stem cells ischemic stroke MIR-34A Nrf2 PROLIFERATION SIRT1 WNT1 β-catenin
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