Mesenchymal progenitor cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a rat cellular cardiomyoplasty model
Mesenchymal progenitor cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a rat cellular cardiomyoplasty model
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DOI：
10.1161/01.cir.0000089186.09692.fa
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发表时间：
2003-09-09
期刊：
影响因子：
37.8
通讯作者：
Kantelip, JP
中科院分区：
文献类型：
--
作者：
Davani, S;Marandin, A;Kantelip, JP
背景：细胞心肌成形术是改善梗死后心功能的一种很有前途的方法。分析了移植间充质祖细胞（MPCs）在大鼠心肌梗死模型中的分化途径及其对左心室功能的影响。方法与结果：采用Lewis大鼠左冠状动脉结扎模型。骨髓细胞粘附法分离MPCs。结扎7天后，将4′，6-二氨基-2′-苯基吲哚标记的MPCs注入梗死心肌（n=8）。对照动物梗死心肌注射培养基（n=8）。植入30天后，免疫荧光研究显示一些植入细胞表达平滑肌表型（α SM肌动蛋白（+）），与培养中观察到的相似。其他移植细胞失去了平滑肌表型，获得了内皮表型（CD31(+)）。此外，与对照组相比，MPC组血管密度增加。30天后，超声心动图显示，与对照组相比，MPCs左心室功能有所改善。结论：在大鼠心肌梗死心脏模型中给药是安全的。一些移植细胞分化为内皮细胞，失去了平滑肌表型。在这种情况下，MPC植入可能有助于改善心功能。
Background-Cellular cardiomyoplasty is a promising approach to improve postinfarcted cardiac function. The differentiation pathways of engrafted mesenchymal progenitor cells (MPCs) and their effects on the left ventricular function in a rat myocardial infarct heart model were analyzed.Methods and Results-A ligation model of left coronary artery of Lewis rats was used. MPCs were isolated by bone marrow cell adherence. Seven days after ligation, MPCs labeled with 4', 6-diamidino-2'-phenylindole were injected into the infarcted myocardium (n=8). Culture medium was injected in the infarcted myocardium of control animals (n=8). Thirty days after implantation, immunofluorescence studies revealed some engrafted cells expressing a smooth muscle phenotype (alpha SM actin(+)), as similarly observed in culture. Other engrafted cells lost their smooth muscle phenotype and acquired an endothelial phenotype (CD31(+)). Furthermore, vessel density was augmented in the MPC group in comparison with the control group. After 30 days, echocardiography showed an improvement on left ventricular performance in the MPCs compared with the control group.Conclusions-In vivo administration of syngenic MPCs into a rat model of myocardial infarcted heart was safety demonstrated. Some engrafted cells appeared to differentiate into endothelial cells and loss their smooth muscle phenotype. MPC engraftment might to contribute to the improvement on the cardiac function in such a setting.