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
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.
