Pretreatment of Human Mesenchymal Stem Cells with Pioglitazone Improved Efficiency of Cardiomyogenic Transdifferentiation and Cardiac Function
Pretreatment of Human Mesenchymal Stem Cells with Pioglitazone Improved Efficiency of Cardiomyogenic Transdifferentiation and Cardiac Function
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DOI：
10.1002/stem.574
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发表时间：
2011-02-01
期刊：
影响因子：
5.2
通讯作者：
Umezawa, Akihiro
中科院分区：
文献类型：
--
作者：
Shinmura, Daisuke;Togashi, Ikuko;Umezawa, Akihiro
默认的人骨髓间充质干细胞（MSC）移植的疗效是适度的。在这项研究中，我们的挑战是通过用吡格列酮预处理MSC来提高MSC体内移植的疗效。在心肌诱导之前，用或不用含有1 μ M吡格列酮的培养基培养MSC。在体外诱导心肌细胞后，用抗心肌肌钙蛋白-I抗体通过免疫细胞化学计算心肌转分化效率（CTE）。对于体内实验，在裸大鼠中制造左心室前部的心肌梗死（MI）。MI后2周，分别注射经吡格列酮（p-BM; n = 30）或未经吡格列酮（BM; n = 17）预处理的MSCs，然后存活2周。通过超声心动图和免疫组织化学方法比较左心室功能，观察体内心肌转分化。用吡格列酮预处理显著增加体外CTE（1.9% +/-0.2%n = 47对39.5% +/-4.7%n = 13，p <0.05）。移植吡格列酮预处理的MSC显著改善了左心室缩短百分比的变化（BM; -4.8% +/-2.1%，vs. p-BM; 5.2% +/-1.5%）。免疫组织化学显示体内p-BM中心肌源性转分化的显著改善（BM; 0% +/-0%n = 5，vs. p-BM; 0.077% +/-0.041%n = 5）。移植吡格列酮预处理的MSC显着改善心脏功能，可以是一个有前途的心脏干细胞来源，预期心肌发生。干细胞2011;29：357-366
The efficacy of transplantation of default human marrow-derived mesenchymal stem cells (MSCs) was modest. In this study, our challenge was to improve the efficacy of MSC transplantation in vivo by pretreatment of MSCs with pioglitazone. MSCs were cultured with or without medium containing 1 mu M of pioglitazone before cardiomyogenic induction. After cardiomyogenic induction in vitro, cardiomyogenic transdifferentiation efficiency (CTE) was calculated by immunocytochemistry using anti-cardiac troponin-I antibody. For the in vivo experiments, myocardial infarction (MI) at the anterior left ventricle was made in nude rats. Two weeks after MI, MSCs pretreated with pioglitazone (p-BM; n = 30) or without pioglitazone (BM; n = 17) were injected, and then survived for 2 weeks. We compared left ventricular function by echocardiogram and immunohistochemistry to observe cardiomyogenic transdifferentiation in vivo. Pretreatment with pioglitazone significantly increased the CTE in vitro (1.9% +/- 0.2% n = 47 vs. 39.5% +/- 4.7% n = 13, p < .05). Transplantation of pioglitazone pretreated MSCs significantly improved change in left ventricular % fractional shortening (BM; -4.8% +/- 2.1%, vs. p-BM; 5.2% +/- 1.5%). Immunohistochemistry revealed significant improvement of cardiomyogenic transdifferentiation in p-BM in vivo (BM; 0% +/- 0% n = 5, vs. p-BM; 0.077% +/- 0.041% n = 5). Transplantation of pioglitazone-pretreated MSCs significantly improved cardiac function and can be a promising cardiac stem cell source to expect cardiomyogenesis. STEM CELLS 2011;29:357-366