Erythropoietin improves the efficiency of endothelial progenitor cell therapy after myocardial infarction in mice: Effects on transplanted cell survival and autologous endothelial progenitor cell mobilization
Erythropoietin improves the efficiency of endothelial progenitor cell therapy after myocardial infarction in mice: Effects on transplanted cell survival and autologous endothelial progenitor cell mobilization
复制标题
促红细胞生成素提高小鼠心肌梗死后内皮祖细胞治疗的效率：对移植细胞存活和自体内皮祖细胞动员的影响
DOI：
10.1016/j.jss.2012.04.047
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发表时间：
2012-07-01
影响因子：
2.2
通讯作者：
Jiang, Shisen
中科院分区：
文献类型：
--
作者：
Cheng, Yan;Hu, Ruoyu;Jiang, Shisen
背景：内皮祖细胞（Endothelial progenitor cells，EPCs）参与血管修复和血管新生.因此，将EPC移植到缺血心肌中可能改善心功能;然而，绝大多数细胞在短时间内死亡。本研究旨在探讨外源性促红细胞生成素（EPO）的交付是否可以提高移植的EPCs的生存和增强效率的EPC为基础的细胞therapy.Methods：心肌梗死在野生型小鼠结扎左冠状动脉前降支诱导。将促红细胞生成素（EPO）和增强型绿色荧光蛋白-内皮祖细胞（EPCs）分别移植于梗死灶周围心肌。术后7 d和28 d检测到增强型绿色荧光蛋白-EPCs。术后3 d和28 d检测循环EPCs的数量。各组间比较心肌梗死灶周围心肌基质细胞衍生因子-1 α和血管内皮生长因子的浓度、微血管密度、细胞凋亡、纤维化和心功能。结果：EPC + EPO组心肌中绿色荧光蛋白-EPCs的表达明显高于单纯EPC组。与单独应用EPC相比，EPC + EPO治疗后循环EPC水平显著升高。基质细胞衍生因子-1 α和血管内皮生长因子相应增加，沿着微血管密度增加，细胞凋亡减少，梗死周围心肌纤维化减少。结论：EPO可提高EPC治疗心肌梗死的效率，并能改善心肌梗死后的左室短轴缩短率，增加心肌梗死后的室间隔厚度。这种效应与增强的移植EPC存活和自体EPC动员有关。(C)2012 Elsevier Inc. All rights reserved.
Background: Endothelial progenitor cells (EPCs) participate in vascular repair and angiogenesis. Thus, EPC transplantation into ischemic myocardium might improve cardiac function; however, the vast majority of cells die within a short period. The present study was designed to investigate whether exogenous erythropoietin (EPO) delivery could improve the survival of transplanted EPCs and enhance the efficiency of EPC-based cell therapy.Methods: Myocardial infarction was induced in wild-type mice by ligating the left anterior descending coronary artery. Enhanced green fluorescent protein-EPCs with or without EPO were transplanted into peri-infarct myocardium. Enhanced green fluorescent protein-EPCs were detected 7 and 28 d after surgery. The amount of circulating EPCs was analyzed 3 and 28 d after surgery. The stromal cell-derived factor-1 alpha and vascular endothelial growth factor concentrations, microvessel density, apoptosis, fibrosis in the peri-infarct myocardium, and cardiac function were compared among the groups.Results: More enhanced green fluorescent protein-EPCs were found in the hearts treated with EPC + EPO than in those treated with EPC alone. The circulating EPC level was markedly elevated after EPC + EPO treatment compared with EPC application alone. Stromal cell-derived factor-1 alpha and vascular endothelial growth factor were increased accordingly, along with increased microvessel density, decreased apoptosis, and reduced fibrosis in the peri-infarct myocardium. Left ventricular fractional shortening was greater and the interventricular septum was thicker after EPC + EPO treatment compared with EPC treatment alone.Conclusions: EPO improved the efficiency of EPC therapy in mice with myocardial infarction. This effect was associated with enhanced transplanted EPC survival and autologous EPC mobilization. (C) 2012 Elsevier Inc. All rights reserved.