VEGF/SDF-1 promotes cardiac stem cell mobilization and myocardial repair in the infarcted heart
VEGF/SDF-1 promotes cardiac stem cell mobilization and myocardial repair in the infarcted heart
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VEGF/SDF-1促进梗死心脏中的心脏干细胞动员和心肌修复
DOI：
10.1093/cvr/cvr053
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发表时间：
2011-08-01
影响因子：
10.8
通讯作者：
Chen, Shi-You
中科院分区：
文献类型：
--
作者：
Tang, Jun-Ming;Wang, Jia-Ning;Chen, Shi-You
本研究的目的是探讨间充质干细胞（MSC）分泌的血管内皮生长因子（VEGF）是否能改善心肌存活和移植的MSC在梗死心脏中的植入，并通过旁分泌释放心肌基质细胞衍生因子-1 α促进干细胞的募集表达VEGF的MSC（（MSC）-M-VEGF）条件培养基通过VEGF和血管内皮生长因子受体（VEGFR）增强心脏切片和H9 C2心肌成肌细胞中的SDF-1 α表达。（MSC）-M-VEGF条件培养基至少部分通过SDF-1 α/CXCR 4途径显著促进心脏干细胞（CSC）迁移，并与VEGFR-1和VEGFR-3结合。在体内，（MSC）-M-VEGF刺激的SDF-1 α在梗死心脏中的表达导致骨髓干细胞和CSC的大量动员和归巢。此外，VEGF诱导的SDF-1 α引导房室沟中外源性引入的CSC迁移到梗死区，导致梗死面积减小。功能研究表明，（MSC）-M-VEGF移植刺激了梗死心脏中广泛的血管平滑肌生成，如心肌肌钙蛋白T、CD 31和血管性血友病因子的表达所示，并改善了左心室性能，而通过RNAi或拮抗剂阻断SDF-1 α或其受体显著降低了（MSC）-M-1的有益作用。结论外源性VEGF至少部分通过SDF-1 α/CXCR 4介导的CSC募集促进心肌修复。
Aims The objective of this study was to investigate whether vascular endothelial growth factor (VEGF) secreted by mesenchymal stem cells (MSC) improves myocardial survival and the engraftment of implanted MSC in infarcted hearts and promotes recruitment of stem cells through paracrine release of myocardial stromal cell-derived factor-1 alpha (SDF-1 alpha).Methods and results VEGF-expressing MSC ((MSC)-M-VEGF)-conditioned medium enhanced SDF-1 alpha expression in heart slices and H9C2 cardio-myoblast cells via VEGF and the vascular endothelial growth factor receptor (VEGFR). The (MSC)-M-VEGF-conditioned medium markedly promoted cardiac stem cell (CSC) migration at least in part via the SDF-1 alpha/CXCR4 pathway and involved binding to VEGFR-1 and VEGFR-3. In vivo, (MSC)-M-VEGF-stimulated SDF-1 alpha expression in infarcted hearts resulted in massive mobilization and homing of bone marrow stem cells and CSC. Moreover, VEGF-induced SDF-1 alpha guided the exogenously introduced CSC in the atrioventricular groove to migrate to the infarcted area, leading to a reduction in infarct size. Functional studies showed that (MSC)-M-VEGF transplantation stimulated extensive angiomyogenesis in infarcted hearts as indicated by the expression of cardiac troponin T, CD31, and von Willebrand factor and improved the left ventricular performance, whereas blockade of SDF-1 alpha or its receptor by RNAi or antagonist significantly diminished the beneficial effects of (MSC)-M-VEGF.Conclusion Exogenously expressed VEGF promotes myocardial repair at least in part through SDF-1 alpha/CXCR4-mediated recruitment of CSC.