Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction

Yoshinori Miyahara; Noritoshi Nagaya; Masaharu Kataoka; Bobby Yanagawa; Koichi Tanaka; Hiroyuki Hao; Kozo Ishino; Hideyuki Ishida; Tatsuya Shimizu; Kenji Kangawa; Shunji Sano; Teruo Okano; Soichiro Kitamura; Hidezo Mori

doi:10.1038/nm1391

Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction

Yoshinori Miyahara, Noritoshi Nagaya, Masaharu Kataoka, Bobby Yanagawa, Koichi Tanaka, Hiroyuki Hao, Kozo Ishino, Hideyuki Ishida, Tatsuya Shimizu, Kenji Kangawa, Shunji Sano, Teruo Okano, Soichiro Kitamura, Hidezo Mori

Research output: Contribution to journal › Article › peer-review

1027 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	459-465
Number of pages	7
Journal	Nature Medicine
Volume	12
Issue number	4
DOIs	https://doi.org/10.1038/nm1391
Publication status	Published - Apr 2006
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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title = "Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction",

abstract = "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.",

author = "Yoshinori Miyahara and Noritoshi Nagaya and Masaharu Kataoka and Bobby Yanagawa and Koichi Tanaka and Hiroyuki Hao and Kozo Ishino and Hideyuki Ishida and Tatsuya Shimizu and Kenji Kangawa and Shunji Sano and Teruo Okano and Soichiro Kitamura and Hidezo Mori",

note = "Funding Information: We thank J.I. Hoffman for his statistical advice. We thank T. Iwase, T. Ito, S. Murakami, N. Sakata and Y. Isono for their technical support. We thank Y. Tsuboi and H. Sonoda for their assistance with microscopic analysis of monolayered cell grafts. We also thank Y. Sawa for his suggestions on this study. This work was supported by research grants for Cardiovascular Disease (16C-6) and Human Genome Tissue Engineering 005 and 009 from the Japanese Ministry of Health, Labor and Welfare, and the Program for Promotion of Fundamental Studies in Health Science of the Japanese National Institute of Biomedical Innovation.",

year = "2006",

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doi = "10.1038/nm1391",

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pages = "459--465",

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T1 - Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction

AU - Miyahara, Yoshinori

AU - Nagaya, Noritoshi

AU - Kataoka, Masaharu

AU - Yanagawa, Bobby

AU - Tanaka, Koichi

AU - Hao, Hiroyuki

AU - Ishino, Kozo

AU - Ishida, Hideyuki

AU - Shimizu, Tatsuya

AU - Kangawa, Kenji

AU - Sano, Shunji

AU - Okano, Teruo

AU - Kitamura, Soichiro

AU - Mori, Hidezo

N1 - Funding Information: We thank J.I. Hoffman for his statistical advice. We thank T. Iwase, T. Ito, S. Murakami, N. Sakata and Y. Isono for their technical support. We thank Y. Tsuboi and H. Sonoda for their assistance with microscopic analysis of monolayered cell grafts. We also thank Y. Sawa for his suggestions on this study. This work was supported by research grants for Cardiovascular Disease (16C-6) and Human Genome Tissue Engineering 005 and 009 from the Japanese Ministry of Health, Labor and Welfare, and the Program for Promotion of Fundamental Studies in Health Science of the Japanese National Institute of Biomedical Innovation.

PY - 2006/4

Y1 - 2006/4

N2 - 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.

AB - 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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Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction

Abstract

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