Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction

Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction
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DOI:
10.1016/j.yjmcc.2007.09.012
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发表时间:
2008-03-01
影响因子:
5
通讯作者:
Willerson, James T.
Willerson, James T.
中科院分区:
医学2区
文献类型:
--
作者:
Penn, Emerson C.;Silva, Guilherme V.;Willerson, James T.

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本研究评估了急性心肌梗死(AMI)后经心内膜(TE)机电导引下移植骨髓间充质干细胞(MSCs)的安全性,并比较了经冠状动脉(IC)移植和TE移植的安全性。在犬急性心肌缺血模型中,于急性心肌梗死后7天经IC和TE途径接种100×106个MSCs。通过二维超声心动图进行功能评估,并进行详细的组织病理学分析,以评估细胞治疗对血管密度和纤维化的影响。并比较了两种给药方式的细胞分布模式。TE组心肌缺血量明显减少(P=0.007)。TE组(21天随访)左心室射血分数(LVEF)平均增加13%,明显优于对照组(P=0.01),IC分娩组无明显改善。IC组和TE组的细胞分布模式不同。本研究提示MSC治疗在急性心肌梗死后可能是安全有效的。在TE和IC治疗的比较中,TE组表现出更高的细胞滞留(甚至在梗死灶的损伤中心),血管增加,功能改善更明显。TE组局部细胞密度较高可能是影响疗效的重要因素。(C)2008 Elsevier Inc.保留所有权利。
This study assessed safety of transendocardial (TE) electromechanical-guided delivery of bone marrow mesenchymal stem cells (MSCs) after acute myocardial infarction (AMI) and compared intracoronary (IC) delivery with TE delivery. In a canine acute myocardial ischemia model, 100 X 106 MSCs were delivered 7 days after AMI via IC and TE routes. Functional assessment was performed by 2D echocardiogram, and detailed histopathologic analyses were performed to assess the impact of cell therapy in vascular density and fibrosis. Patterns of cell distribution in both delivery methods were also compared. There was a statistically significant reduction in the amount of myocardial ischemia in the TE group (P=0.007). Left ventricular ejection fraction (LVEF) increased 13% (mean) in the TE group (21-day follow-up) and was significantly better than that of the controls (P=0.01), but did not improve in the IC-delivery group. Dissimilar patterns of cell distribution were noted between the IC and TE groups. This study suggests that MSC treatment is probably safe and effective after AMI In the comparison of TE and IC delivery, the TE group showed higher cell retention (clusters even in the injury center of the infarct) with an increased vascularity and greater functional improvement than did the IC group (no clusters; cells at the border of the infarct). The higher local cell density in the TE group may be important for therapeutic effectiveness. (C) 2008 Elsevier Inc. All rights reserved.