Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction.
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.
Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
Yoshinori
Y
Miyahara
Noritoshi
N
Nagaya
Masaharu
M
Kataoka
Bobby
B
Yanagawa
Koichi
K
Tanaka
Hiroyuki
H
Hao
Kozo
K
Ishino
Hideyuki
H
Ishida
Tatsuya
T
Shimizu
Kenji
K
Kangawa
Shunji
S
Sano
Teruo
T
Okano
Soichiro
S
Kitamura
Hidezo
H
Mori
D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004452:Echocardiography; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007211:Indoles; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D018613:Microscopy, Confocal; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology* / Q000601:surgery / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D019089:Stem Cell Factor / Q000378:metabolism; D015996:Survival Rate; D019076:Transgenes
D005456:Fluorescent Dyes; D007211:Indoles; D019089:Stem Cell Factor; D049452:Green Fluorescent Proteins; C007293:DAPI