Bone marrow mesenchymal stem cells(MSCs)are considered as a promising cell source to treat the acute myocardial infarction.However,over 90%of the stem cells usually die in the first three days of transplantation.Survi...Bone marrow mesenchymal stem cells(MSCs)are considered as a promising cell source to treat the acute myocardial infarction.However,over 90%of the stem cells usually die in the first three days of transplantation.Survival potential,migration ability and paracrine capacity have been considered as the most important three factors for cell transplantation in the ischemic cardiac treatment.We hypothesized that stromal-derived factor-1(SDF-1)/CXCR4 axis plays a critical role in the regulation of these processes.In this study,apoptosis was induced by exposure of MSCs to H2O2 for 2 h.After re-oxygenation,the SDF-1 pretreated MSCs demonstrated a significant increase in survival and proliferation.SDF-1 pretreatment also enhanced the migration and increased the secretion of pro-survival and angiogenic cytokines including basic fibroblast growth factor and vascular endothelial growth factor.Western blot and RT-PCR demonstrated that SDF-1 pretreatment significantly activated the pro-survival Akt and Erk signaling pathways and up-regulated Bcl-2/Bax ratio.These protective effects were partially inhibited by AMD3100,an antagonist of CXCR4.We conclude that the SDF-1/CXCR4 axis is critical for MSC survival,migration and cytokine secretion.展开更多
目的:探讨补肾益髓生血法再生障碍性贫血(AA)大鼠含药血清通过SDF-1/CXCR4介导的PI3K/AKT信号通路对骨髓间充质干细胞(BMSCs)与骨髓单个核细胞(BMNCs)共培养BMNCs增殖能力的影响。方法:60Co-γ联合CTX建立再障大鼠模型,各组按文献方法...目的:探讨补肾益髓生血法再生障碍性贫血(AA)大鼠含药血清通过SDF-1/CXCR4介导的PI3K/AKT信号通路对骨髓间充质干细胞(BMSCs)与骨髓单个核细胞(BMNCs)共培养BMNCs增殖能力的影响。方法:60Co-γ联合CTX建立再障大鼠模型,各组按文献方法分离血清冻存备用。在分别建立粒系和红系BMSCs与BMNCs共培养体系基础上,用补肾益髓生血法再障大鼠含药血清进行干预。实验分为空白对照组、正常对照组、模型组、康力龙组、滋肾生血组、益髓生血组和温肾生血组。于第4、8、10天分别计数红系集落形成单位(CFU-E)、粒-单核细胞系集落形成单位(CFU-GM)、红系爆式集落形成单位(BFU-E)。共培养10d后,提取细胞总RNA,RT-PCR检测SDF-1、CXCR4、PI3K、AKT与m TOR m RNA的表达。结果:补肾益髓生血法含药血清促进了共培养BMNCs的增殖分化,其集落形成数目显示各治疗组CFU-E、BFU-E、CFU-GM集落形成数量较模型组增加(P<0.05,P<0.01);RT-PCR结果显示康力龙组、滋肾生血组、益髓生血组、温肾生血组SDF-1、CXCR4、PI3K、AKT、m TOR表达较模型组显著升高(P<0.05,P<0.01),集落形成与基因表达均显示,滋肾生血组优于温肾生血组和益髓生血组(P<0.05,P<0.01)。结论:补肾益髓生血法AA大鼠含药血清可以促进BMSCs与BMNCs共培养体系中BMNCs的增殖分化,这可能与SDF-1/CXCR4介导的PI3K/AKT信号通路有关,其中滋肾生血法优于益髓生血法和温肾生血法。展开更多
基金by the National key Basic Research Program of China(Grant Nos.2011CB964903 and 2011CB606202)the National Outstanding Youth Foundation(No.30725030)+1 种基金the National Natural Science Foundation of China(Grant Nos.30570471 and 30970746)the National Key Scientific Program of China(No.952010).
文摘Bone marrow mesenchymal stem cells(MSCs)are considered as a promising cell source to treat the acute myocardial infarction.However,over 90%of the stem cells usually die in the first three days of transplantation.Survival potential,migration ability and paracrine capacity have been considered as the most important three factors for cell transplantation in the ischemic cardiac treatment.We hypothesized that stromal-derived factor-1(SDF-1)/CXCR4 axis plays a critical role in the regulation of these processes.In this study,apoptosis was induced by exposure of MSCs to H2O2 for 2 h.After re-oxygenation,the SDF-1 pretreated MSCs demonstrated a significant increase in survival and proliferation.SDF-1 pretreatment also enhanced the migration and increased the secretion of pro-survival and angiogenic cytokines including basic fibroblast growth factor and vascular endothelial growth factor.Western blot and RT-PCR demonstrated that SDF-1 pretreatment significantly activated the pro-survival Akt and Erk signaling pathways and up-regulated Bcl-2/Bax ratio.These protective effects were partially inhibited by AMD3100,an antagonist of CXCR4.We conclude that the SDF-1/CXCR4 axis is critical for MSC survival,migration and cytokine secretion.
文摘目的:探讨补肾益髓生血法再生障碍性贫血(AA)大鼠含药血清通过SDF-1/CXCR4介导的PI3K/AKT信号通路对骨髓间充质干细胞(BMSCs)与骨髓单个核细胞(BMNCs)共培养BMNCs增殖能力的影响。方法:60Co-γ联合CTX建立再障大鼠模型,各组按文献方法分离血清冻存备用。在分别建立粒系和红系BMSCs与BMNCs共培养体系基础上,用补肾益髓生血法再障大鼠含药血清进行干预。实验分为空白对照组、正常对照组、模型组、康力龙组、滋肾生血组、益髓生血组和温肾生血组。于第4、8、10天分别计数红系集落形成单位(CFU-E)、粒-单核细胞系集落形成单位(CFU-GM)、红系爆式集落形成单位(BFU-E)。共培养10d后,提取细胞总RNA,RT-PCR检测SDF-1、CXCR4、PI3K、AKT与m TOR m RNA的表达。结果:补肾益髓生血法含药血清促进了共培养BMNCs的增殖分化,其集落形成数目显示各治疗组CFU-E、BFU-E、CFU-GM集落形成数量较模型组增加(P<0.05,P<0.01);RT-PCR结果显示康力龙组、滋肾生血组、益髓生血组、温肾生血组SDF-1、CXCR4、PI3K、AKT、m TOR表达较模型组显著升高(P<0.05,P<0.01),集落形成与基因表达均显示,滋肾生血组优于温肾生血组和益髓生血组(P<0.05,P<0.01)。结论:补肾益髓生血法AA大鼠含药血清可以促进BMSCs与BMNCs共培养体系中BMNCs的增殖分化,这可能与SDF-1/CXCR4介导的PI3K/AKT信号通路有关,其中滋肾生血法优于益髓生血法和温肾生血法。
