Enhanced therapeutic effects of mesenchymal stem cells on myocardial infarction by ischemic postconditioning through paracrine mechanisms in rats
Enhanced therapeutic effects of mesenchymal stem cells on myocardial infarction by ischemic postconditioning through paracrine mechanisms in rats
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DOI：
10.1016/j.yjmcc.2011.06.013
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发表时间：
2011-11-01
影响因子：
5
通讯作者：
Wang, Weiwei
中科院分区：
文献类型：
--
作者：
Fang, Jun;Chen, Lianglong;Wang, Weiwei
缺血后适应（IPC）对心肌缺血再灌注损伤具有保护作用，缺血再灌注损伤会损害心肌微环境，降低移植细胞的存活率。我们验证了IPC可能改善移植细胞的存活并增强其治疗效果的假设。本研究用携带绿色荧光蛋白（GFP）基因的慢病毒感染Sprague-Dawley大鼠骨髓间充质干细胞（BMSCs）。阻断大鼠左主干冠状动脉缺血30 min，再灌注72 h或28 d。采用10 s再灌注和持续再灌注前10 s缺血3个周期诱导IPC。再灌注2 h时，心肌内注射GFP-BMSCs。在移植后70 h，通过ELISA、PCR或western blotting检测，IPC处理使白细胞介素-10、b细胞白血病-淋巴瘤-2 （BCL-2）、血管内皮细胞和碱性成纤维细胞生长因子（VEGF和bFGF）水平升高，肿瘤坏死因子- α、白细胞介素-1 β和BCL-2相关X蛋白水平降低。通过荧光染色，IPC治疗BMSCs比单独治疗BMSCs产生更多存活的gfp阳性细胞[在70小时，(90 +/- 14)/mm(2) vs (61 +/- 12)/mm(2)，在28天，(55 +/- 14)/mm(2) vs (26 +/- 8)/mm(2)， P
Ischemic postconditioning (IPC) is cardioprotective against ischemia-reperfusion injury which impairs the myocardial micro-environment and reduces the survival of transplanted cells. We tested the hypothesis that IPC may improve the survival of transplanted cells and enhance their therapeutic effects. In this study, bone marrow-derived mesenchymal stem cells (BMSCs) from Sprague-Dawley rats were infected with lentivirus carrying green fluorescent protein (GFP) gene. The left main coronary arteries of rats were occluded for a 30-min ischemia, followed by a 72 h or 28 d reperfusion. IPC was induced by 3 cycles of 10 s reperfusion and 10 s ischemia before sustained reperfusion. GFP-BMSCs were intramyocardially injected at 2 h reperfusion. At 70 h after transplantation, IPC treatment increased the level of interleukin-10, B-cell leukemia-lymphoma-2 (BCL-2), and vascular endothelial and basic fibroblast growth factor (VEGF and bFGF), and decreased the level of tumor necrosis factor-alpha, interleukin-1 beta and BCL-2-associated X protein by ELISA or PCR or western blotting. The BMSCs therapy with IPC produced more surviving GFP-positive cells than the BMSCs therapy alone by fluorescent staining [at 70 h, (90 +/- 14)/mm(2) vs. (61 +/- 12)/mm(2), and at 28 days, (55 +/- 14)/mm(2) vs. (26 +/- 8)/mm(2), P