Route of Delivery Modulates the Efficacy of Mesenchymal Stem Cell Therapy for Myocardial Infarction: A Meta-Analysis of Preclinical Studies and Clinical Trials.
Route of Delivery Modulates the Efficacy of Mesenchymal Stem Cell Therapy for Myocardial Infarction: A Meta-Analysis of Preclinical Studies and Clinical Trials.
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DOI：
10.1161/circresaha.116.309819
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发表时间：
2017-03-31
影响因子：
20.1
通讯作者：
Hare JM
中科院分区：
文献类型：
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作者：
Kanelidis AJ;Premer C;Lopez J;Balkan W;Hare JM
积累的数据支持间充质干细胞（MSC）疗法的治疗作用;然而，在最佳递送途径上没有达成共识。我们检验了MSC递送途径影响梗死面积（IS）减少和左心室射血分数（LVEF）改善的假设。我们进行了一项荟萃分析，调查MSC治疗在急性心肌梗死（AMI）和慢性缺血性心肌病（ICM）临床前研究（58项研究; n=1165只小鼠、大鼠、猪）中的作用，结果显示所有动物模型中IS减少，LVEF改善。在AMI猪研究和临床试验（6项临床试验; n=334例患者）中分析了递送途径。在AMI猪研究中，经内皮干细胞注射（TESI）降低了IS（n=49，9.4%降低95%CI −15.9，−3.0），而心肌内注射（DI）、静脉内输注（IV）和冠状动脉内输注（IC）均无改善。同样，TESI改善了LVEF（n=65，95%CI增加9.1%，3.7，14.5），DI和IV也是如此，而IC没有改善。在人体中，LVEF的变化与这些结果相反，TESI改善了LVEF（n=46，增加7.0%，95%CI 2.7，11.3），IV也是如此，但IC再次证明没有改善。MSC治疗改善了AMI和ICM动物模型的心功能。在AMI猪研究和临床试验中，递送途径似乎在调节MSC治疗的疗效方面发挥作用，表明TESI由于其减少IS和改善LVEF而具有优越性，这对未来研究的设计具有重要意义。
Accumulating data supports a therapeutic role for mesenchymal stem cell (MSC) therapy; however, there is no consensus on the optimal route of delivery. We tested the hypothesis that the route of MSC delivery influences the reduction in infarct size (IS) and improvement in left ventricular ejection fraction (LVEF). We performed a meta-analysis investigating the effect of MSC therapy in acute myocardial infarction (AMI) and chronic ischemic cardiomyopathy (ICM) preclinical studies (58 studies; n=1165 mouse, rat, swine) which revealed a reduction in IS and improvement of LVEF in all animal models. Route of delivery was analyzed in AMI swine studies and clinical trials (6 clinical trials; n=334 patients). In AMI swine studies, transendocardial stem cell injection (TESI) reduced IS (n=49, 9.4% reduction 95%CI −15.9, −3.0), whereas intramyocardial injection (DI), intravenous infusion (IV), and intracoronary infusion (IC) indicated no improvement. Similarly, TESI improved LVEF (n=65, 9.1% increase 95%CI 3.7, 14.5), as did DI and IV, while IC demonstrated no improvement. In humans, changes of LVEF paralleled these results, with TESI improving LVEF (n=46, 7.0% increase 95%CI 2.7, 11.3), as did IV, but again IC demonstrating no improvement. MSC therapy improves cardiac function in animal models of both AMI and ICM. The route of delivery appears to play a role in modulating the efficacy of MSC therapy in AMI swine studies and clinical trials, suggesting the superiority of TESI due to its reduction in IS and improvement of LVEF, which has important implications for the design of future studies.