Transplantation of cardiac progenitor cells ameliorates cardiac dysfunction after myocardial infarction in mice

被引:195
作者
Matsuura, Katsuhisa [1 ,2 ]
Honda, Atsushi
Nagai, Toshio [3 ]
Fukushima, Noritoshi
Iwanaga, Koji [3 ]
Tokunaga, Masakuni [3 ]
Shimizu, Tatsuya [2 ]
Okano, Teruo [2 ]
Kasanuki, Hiroshi
Hagiwara, Nobuhisa
Komuro, Issei [3 ]
机构
[1] Tokyo Womens Med Univ, Dept Cardiol, Shinjuku Ku, Tokyo 1628666, Japan
[2] Tokyo Womens Med Univ, Inst Adv Biomed Engn & Sci, Tokyo 1628666, Japan
[3] Chiba Univ, Grad Sch Med, Dept Cardiovasc Sci & Med, Chiba 2608670, Japan
关键词
ALPHA-CONVERTING ENZYME; NECROSIS-FACTOR-ALPHA; BONE-MARROW; STEM-CELLS; ADHESION MOLECULE-1; REPAIR; HEART; CARDIOMYOCYTES; SURVIVAL; DIFFERENTIATION;
D O I
10.1172/JCI37456
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Cardiac progenitor cells are a potential source of cell therapy for heart failure. Although recent studies have shown that transplantation of cardiac stem/progenitor cells improves function of infarcted hearts, the precise mechanisms of the improvement in function remain poorly understood. The present study demonstrates that transplantation of sheets of clonally expanded stem cell antigen 1-positive (Sca-1-positive) cells (CPCs) ameliorates cardiac dysfunction after myocardial infarction in mice. CPC efficiently differentiated into cardiomyocytes and secreted various cytokines, including soluble VCAM-1 (sVCAM-1). Secreted sVCAM-1 induced migration of endothelial cells and CPCs and prevented cardiomyocyte death from oxidative stress through activation of Akt, ERK, and p38 MAPK. Treatment with antibodies specific for very late antigen-4 (VLA-4), a receptor of sVCAM-1, abolished the effects of CPC-derived conditioned medium on cardiomyocytes and CPCs in vitro and inhibited angiogenesis, CPC migration, and survival in vivo, which led to attenuation of improved cardiac function following transplantation of CPC sheets. These results suggest that CPC transplantation improves cardiac function. after myocardial infarction through cardiomyocyte differentiation and paracrine mechanisms mediated via the sVCAM-1/VLA-4 signaling pathway.
引用
收藏
页码:2204 / 2217
页数:14
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