Nature Medicine
- 12, 459 - 465 (2006)
Published online: 2 April 2006; | doi:10.1038/nm1391
Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarctionYoshinori Miyahara1, 9, Noritoshi Nagaya1, 9, Masaharu Kataoka1, Bobby Yanagawa1, Koichi Tanaka1, Hiroyuki Hao2, Kozo Ishino3, Hideyuki Ishida4, Tatsuya Shimizu5, Kenji Kangawa6, Shunji Sano3, Teruo Okano5, Soichiro Kitamura7 & Hidezo Mori81
Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan. 2
Department of Pathology, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan. 3
Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8555, Japan. 4
Department of Physiology, School of Medicine, Tokai University, Bohseidai, Isehara, Kanagawa, 259-1193, Japan. 5
Institute of Advanced Biomedical Engineering and Science, Tokyo Woman's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. 6
Department of Biochemistry, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan. 7
Department of Cardiovascular Surgery, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan. 8
Department of Cardiac Physiology, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan. 9
These authors contributed equally to this work.
Correspondence should be addressed to Noritoshi Nagaya nnagaya@ri.ncvc.go.jp or Hidezo Mori hidemori@ri.ncvc.go.jp 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.
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