Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction

被引:907
|
作者
Miyahara, Y
Nagaya, N
Kataoka, M
Yanagawa, B
Tanaka, K
Hao, H
Ishino, K
Ishida, H
Shimizu, T
Kangawa, K
Sano, S
Okano, T
Kitamura, S
Mori, H
机构
[1] Natl Cardiovasc Ctr, Dept Regenerat Med & Tissue Engn, Res Inst, Suita, Osaka 5658565, Japan
[2] Natl Cardiovasc Ctr, Dept Pathol, Suita, Osaka 5658565, Japan
[3] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cardiovasc Surg, Okayama 7008555, Japan
[4] Tokai Univ, Sch Med, Dept Physiol, Isehara, Kanagawa 2591193, Japan
[5] Tokyo Womens Med Univ, Inst Adv Biomed Engn & Sci, Shinjuku Ku, Tokyo 1628666, Japan
[6] Natl Cardiovasc Ctr, Dept Biochem, Res Inst, Suita, Osaka 5658565, Japan
[7] Natl Cardiovasc Ctr, Dept Cardiovasc Surg, Suita, Osaka 5658565, Japan
[8] Natl Cardiovasc Ctr, Res Inst, Dept Cardiac Physiol, Suita, Osaka 5658565, Japan
关键词
D O I
10.1038/nm1391
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mesenchymal stem cells are multipotent cells that can differentiate into cardiomyocytes and vascular endothelial cells. Here we show, using cell sheet technology, that monolayered mesenchymal stem cells have multipotent and self-propagating properties after transplantation into infarcted rat hearts. We cultured adipose tissue-derived mesenchymal stem cells characterized by flow cytometry using temperature-responsive culture dishes. Four weeks after coronary ligation, we transplanted the monolayered mesenchymal stem cells onto the scarred myocardium. After transplantation, the engrafted sheet gradually grew to form a thick stratum that included newly formed vessels, undifferentiated cells and few cardiomyocytes. The mesenchymal stem cell sheet also acted through paracrine pathways to trigger angiogenesis. Unlike a fibroblast cell sheet, the monolayered mesenchymal stem cells reversed wall thinning in the scar area and improved cardiac function in rats with myocardial infarction. Thus, transplantation of monolayered mesenchymal stem cells may be a new therapeutic strategy for cardiac tissue regeneration.
引用
收藏
页码:459 / 465
页数:7
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