间充质干细胞通过旁分泌效应激活心脏干细胞迁移(英文)

目的:探索移植到心梗部位的间充质干细胞是否通过其旁分泌效应促进心脏干细胞迁移至心梗部位。方法:间充质干细胞(MSC)特征经流式细胞术鉴定其表面标志物特征及多向诱导分化实验确认其干性。经体外Transwell分析心脏干细胞迁移特征,利用VEGF,HGF及SDF-1α等受体特异阻断剂观察其在心脏干细胞迁移中的作用。在体利用左冠状动脉前降之结扎法复制心肌梗死模型。心梗后7 d,植入MSC到心梗及周边部位。细胞移植7 d后,流式细胞术分析其外周血中c-kit阳性的干细胞含量,免疫荧光组织化学技术分析心梗部位c-kit阳性的干细胞数目,同时行Western Blot分析心脏VEGF,HGF及SDF-1α的表达,一月后心导管技术测量心功能及胶原染色和HE染色确定梗死面积。结果:移植的MSC增加了心梗部位VEGF,HGF及SDF-1α的表达,并动员c-kit阳性的干细胞迁移至心梗部位。与对照组相比,MSC移植组明显降低了心梗面积,显著增加了血管密度,明显改善了左室心脏功能。体外迁移实验发现MSC条件培养基能够诱导心脏干细胞迁移,这个过程能被VEGFR、CXCR4及c-Met等受体特异阻断剂所阻断,且c-Met可能起主要作用。结论:移植的MSC通过其旁分泌效应激活c-kit阳性的干细胞迁移至心梗部位修复受损的心脏。

Mesenchymal Stem Cell: Paracrine Effect on Cardiac Stem Cell Migration

Objective To test the hypothesis that mesenchymal stem cells(MSCs) in infarcted hearts promote recruitment of stem cells through their paracrine effect.Methods MSCs were identified by the expression of cell surface markers using flow cytometry and multi-differentiation potential.Cardiac stem cell(CSC) migration was analyzed by in vitro transwell migration assay.The signaling pathways important for CSC migration were identified by specific receptor blockers.Myocardium infarction(MI) was achieved by ligation of the left anterior descending coronary artery(LAD).MSCs transplant were carried out by injection with a 30-gauge tuberculin syringe separately into four sites for each MI heart.c-kit positive cells in the infarcted hearts and peripheral blood were detected by immunohistochemical fluorescence and flow cytometry.VEGF,HGF and SDF-1α expression were analyzed by Western Blotting.Results MSCs increased the expression of VEGF,SDF-1 and HGF in the infracted myocardium and promoted the massive mobilization and homing of c-kit positive stem cells into infarcted hearts.Infarction size was significantly reduced in MSC-transplantation group compared with the control group.In addition,extensive angiogenesis was observed in the infarcted hearts with MSC transplantation as shown by vWFVIII staining.Importantly,left ventricular function was also significantly improved in the MSC group as compared with the control group.In vitro studies demonstrated that the migration of c-kit positive CSCs was mediated by VEGFR,CXCR4 and c-Met signaling.Conclusion MSC transplantation induced c-kit positive cells trafficking via paracrine effect of MSCs,leading to an improved myocardial repair.