title: Dedifferentiated fat cells convert to cardiomyocyte phenotype and repair infarcted cardiac tissue in rats.
abstract: Adipose tissue-derived stem cells have been demonstrated to differentiate into cardiomyocytes and vascular endothelial cells. Here we investigate whether mature adipocyte-derived dedifferentiated fat (DFAT) cells can differentiate to cardiomyocytes in vitro and in vivo by establishing DFAT cell lines via ceiling culture of mature adipocytes. DFAT cells were obtained by dedifferentiation of mature adipocytes from GFP-transgenic rats. We evaluated the differentiating ability of DFAT cells into cardiomyocytes by detection of the cardiac phenotype markers in immunocytochemical and RT-PCR analyses in vitro. We also examined effects of the transplantation of DFAT cells into the infarcted heart of rats on cardiomyocytes regeneration and angiogenesis. DFAT cells expressed cardiac phenotype markers when cocultured with cardiomyocytes and also when grown in MethoCult medium in the absence of cardiomyocytes, indicating that DFAT cells have the potential to differentiate to cardiomyocyte lineage. In a rat acute myocardial infarction model, transplanted DFAT cells were efficiently accumulated in infarcted myocardium and expressed cardiac sarcomeric actin at 8 weeks after the cell transplantation. The transplantation of DFAT cells significantly (p<0.05) increased capillary density in the infarcted area when compared with hearts from saline-injected control rats. We demonstrated that DFAT cells have the ability to differentiate to cardiomyocyte-like cells in vitro and in vivo. In addition, transplantation of DFAT cells led to neovascuralization in rats with myocardial infarction. We propose that DFAT cells represent a promising candidate cell source for cardiomyocyte regeneration in severe ischemic heart disease.
authors.affiliation: Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Medet
authors.initials: M
authors.lastname: Jumabay
authors.forename: Taro
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kano
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kusumi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Masuko
authors.forename: Masako
authors.initials: M
authors.lastname: Mitsumata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirayama
authors.forename: Hideo
authors.initials: H
authors.lastname: Mugishima
authors.forename: Noboru
authors.initials: N
authors.lastname: Fukuda
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D000818:Animals; D054337:Cell Dedifferentiation / Q000502:physiology*; D017690:Cell Transplantation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D009203:Myocardial Infarction / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction