Myogenic endothelial cells purified from human skeletal muscle improve cardiac function after transplantation into infarcted myocardium.

Myogenic endothelial cells purified from human skeletal muscle improve cardiac function after transplantation into infarcted myocardium.
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DOI:
10.1016/j.jacc.2008.07.064
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发表时间:
2008-12-02
影响因子:
24
通讯作者:
Huard, Johnny
Huard, Johnny
中科院分区:
医学1区
文献类型:
--
作者:
Okada, Masaho;Payne, Thomas R.;Zheng, Bo;Oshima, Hideki;Momoi, Nobuo;Tobita, Kimimasa;Keller, Bradley B.;Phillippi, Julie A.;Peault, Bruno;Huard, Johnny

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目的是评估人骨骼肌来源的肌内皮细胞用于心肌梗死修复的治疗潜力。我们最近从人骨骼肌中鉴定并纯化了一种新的肌内皮细胞群。这些细胞共表达肌源性和内皮细胞标志物,当注射到心脏毒素损伤的骨骼肌中时,产生强大的肌肉再生。使用荧光激活细胞分选仪沿着从人骨骼肌活检组织中分离出肌内皮细胞以及常规成肌细胞和内皮细胞。在雄性免疫缺陷小鼠中诱导急性心肌梗死,并将细胞直接注射到缺血区域。心脏功能通过超声心动图评估,供体细胞植入、血管生成、瘢痕组织、内源性心肌细胞增殖和凋亡均通过免疫组织化学评估。与注射成肌细胞或内皮细胞的心脏相比,心肌内注射肌内皮细胞后观察到左心室功能有更大的改善。移植的肌内皮细胞在梗死心肌内产生了强大的植入,并且还比移植的成肌细胞或内皮细胞更有效地刺激血管生成、瘢痕组织的衰减以及内源性心肌细胞的增殖和存活。我们的研究结果表明,肌内皮细胞代表了一种新的细胞群体,从人类骨骼肌,可能持有的承诺,心脏修复。
The aim was to evaluate the therapeutic potential of human skeletal muscle-derived myoendothelial cells for myocardial infarct repair. We have recently identified and purified a novel population of myoendothelial cells from human skeletal muscle. These cells co-express myogenic and endothelial cell markers and produce robust muscle regeneration when injected into cardiotoxin-injured skeletal muscle. Myoendothelial cells were isolated from biopsies of human skeletal muscle using a fluorescence-activated cell sorter along with populations of regular myoblasts and endothelial cells. Acute myocardial infarction was induced in male immune-deficient mice, and cells were directly injected into the ischemic area. Cardiac function was assessed by echocardiography, and donor cell engraftment, angiogenesis, scar tissue, endogenous cardiomyocyte proliferation and apoptosis were all evaluated by immunohistochemistry. A greater improvement in left ventricular function was observed after intramyocardial injection of myoendothelial cells when compared to hearts injected with myoblast or endothelial cells. Transplanted myoendothelial cells generated robust engraftments within the infarcted myocardium, and also stimulated angiogenesis, attenuation of scar tissue and proliferation and survival of endogenous cardiomyocytes more effectively than transplanted myoblasts or endothelial cells. Our findings suggest that myoendothelial cells represent a novel cell population from human skeletal muscle that may hold promise for cardiac repair.
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