Myogenic Endothelial Cells Purified From Human Skeletal Muscle Improve Cardiac Function After Transplantation Into Infarcted Myocardium

被引:71
作者
Okada, Masaho [1 ,3 ]
Payne, Thomas R. [1 ,3 ,5 ]
Zheng, Bo [1 ,3 ]
Oshima, Hideki [1 ,3 ]
Momoi, Nobuo [2 ]
Tobita, Kimimasa [2 ,5 ]
Keller, Bradley B. [2 ]
Phillippi, Julie A. [1 ,6 ]
Peault, Bruno [1 ,2 ]
Huard, Johnny [1 ,3 ,4 ,5 ]
机构
[1] Childrens Hosp Pittsburgh, Stem Cell Res Ctr, Pittsburgh, PA 15213 USA
[2] Childrens Hosp Pittsburgh, Dept Pediat, Pittsburgh, PA 15213 USA
[3] Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Pittsburgh, PA 15261 USA
[4] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA
[5] Univ Pittsburgh, Sch Med, Dept Bioengn, Pittsburgh, PA USA
[6] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA
关键词
human stem cells; myocardial infarction; paracrine factors; skeletal muscle; VEGF;
D O I
10.1016/j.jacc.2008.07.064
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
Objectives The aim of this study was to evaluate the therapeutic potential of human skeletal muscle-derived myoendothelial cells for myocardial infarct repair. Background We have recently identified and purified a novel population of myoendothelial cells from human skeletal muscle. These cells coexpress myogenic and endothelial cell markers and produce robust muscle regeneration when injected into cardiotoxin-injured skeletal muscle. Methods 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. Results A greater improvement in left ventricular function was observed after intramyocardial injection of myoendothelial cells when compared with that seen in 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. Conclusions Our findings suggest that myoendothelial cells represent a novel cell population from human skeletal muscle that may hold promise for cardiac repair. (J Am Coll Cardiol 2008; 52: 1869-80) (c) 2008 by the American College of Cardiology Foundation
引用
收藏
页码:1869 / 1880
页数:12
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