title: Smooth muscle cell sheet transplantation preserve cardiac function and minimize cardiac remodeling in a rat myocardial infarction model.
abstract: BACKGROUND
  We examined whether a vascular smooth muscle cell (SMC) sheet is effective in the treatment of a rat myocardial infarction (MI) model.
  
  
  METHODS
  We examined the effect of SMC sheet on the cardiac function and cardiac remodeling in a rat MI model in comparison with their effect of dermal fibroblast (DFB) sheet in vivo. Furthermore, we estimated the apoptosis and secretion of angiogenic factor of SMC under hypoxic condition in comparison with DFB. Seven days after MI, monolayer cell sheets were transplanted on the infarcted area (SMC transplantation group, SMC-Tx; DFB transplantation group, DFB-Tx; no cell sheet transplantation group, Untreated; neither MI nor cell sheet transplantation group, Sham). We evaluated cardiac function by echocardiogram, degree of cardiac remodeling by histological examination, and secretion of angiogenic growth factor by enzyme immunoassay.
  
  
  RESULTS
  Twenty-eight days after transplantation, SMC-Tx showed the following characteristics compared with the other groups: 1) significantly greater fractional area shortening (SMC-Tx, 32.3 ± 2.1 %; DFB-Tx, 23.3 ± 2.1 %; untreated, 25.1 ± 2.6 %), 2) suppressed left ventricular dilation, smaller scar expansion, and preserved wall thickness of the area at risk and the posterior wall, 3) decreased fibrosis, preserved myocardium in the scar area, and greater number of arterioles in border-zone, 4) tight attachment of SMC sheets on the scarred myocardium, and less apoptotic cell death. In in vitro experiments, SMCs secreted higher amounts of basic fibroblast growth factor (SMC, 157.7 ± 6.4 pg/ml; DFB, 3.1 ± 1.0 pg/ml), and showed less apoptotic cell death under hypoxia.
  
  
  CONCLUSIONS
  Our results illustrate that transplantation of SMC sheets inhibited the progression of cardiac remodeling and improve cardiac function. These beneficial effects may be due to superior SMC survival.
authors: Division of Organ Regeneration Surgery, Department of Surgery, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan.|Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science, Yonago, Japan.
authors: Shingo
authors: S
authors: Harada
authors: Division of Organ Regeneration Surgery, Department of Surgery, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan.
authors: Yoshinobu
authors: Y
authors: Nakamura
authors: Division of Organ Regeneration Surgery, Department of Surgery, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan.
authors: Suguru
authors: S
authors: Shiraya
authors: Division of Organ Regeneration Surgery, Department of Surgery, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan.
authors: Yoshikazu
authors: Y
authors: Fujiwara
authors: Division of Organ Regeneration Surgery, Department of Surgery, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan.
authors: Yuichiro
authors: Y
authors: Kishimoto
authors: Division of Organ Regeneration Surgery, Department of Surgery, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan.
authors: Takeshi
authors: T
authors: Onohara
authors: Division of Organ Regeneration Surgery, Department of Surgery, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan.
authors: Yuki
authors: Y
authors: Otsuki
authors: Division of Organ Regeneration Surgery, Department of Surgery, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan.
authors: Satoru
authors: S
authors: Kishimoto
authors: Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science, Yonago, Japan.
authors: Yasutaka
authors: Y
authors: Yamamoto
authors: Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science, Yonago, Japan.
authors: Ichiro
authors: I
authors: Hisatome
authors: Division of Organ Regeneration Surgery, Department of Surgery, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan. nishimur@med.tottori-u.ac.jp.
authors: Motonobu
authors: http://orcid.org/0000-0001-8203-6389
authors: M
authors: Nishimura
mesh_terms: D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004452:Echocardiography; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005347:Fibroblasts / Q000637:transplantation; D005355:Fibrosis; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009203:Myocardial Infarction / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000637:transplantation*; D051381:Rats; D012867:Skin / Q000166:cytology; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000503:physiopathology*; D020257:Ventricular Remodeling
chemical_list: D016222:Fibroblast Growth Factor 2
keywords: Cell sheet; Cell survival; Myocardial infarction; Smooth muscle cells