title: Impaired myocardium regeneration with skeletal cell sheets--a preclinical trial for tissue-engineered regeneration therapy.
abstract: BACKGROUND
  We hypothesized that autologous skeletal cell (SC) sheets regenerate the infract myocardium in porcine heart as a preclinical trial.
  
  
  RESULTS
  The impaired heart was created by implantation of ameroid constrictor on left anterior descending for 4 weeks. SCs isolated from leg muscle were cultured and detached from the temperature-responsive domain-coated dishes as single monolayer cell sheet at 20 degrees C. The following therapies were conducted: SC sheets (SC group, n=5); sham (C group n=5). Echocardiography demonstrated that cardiac performance was significantly improved in the SC group 3 and 6 months after operation (fractional area shortening, 3 months; SC vs. C=49.5+/-2.8 vs. 24.6+/-2.0%, P<0.05) and left ventricle dilatation was well attenuated in the SC group. Color kinesis index showed that distressed regional diastolic and systolic function in infarcted anterior wall was significantly recovered (SC vs. C=57.4+/-8.6 vs. 30.2+/-4.7%, P<0.05, diastolic: 58.5+/-4.5 vs. 35.4+/-6.6%, P<0.05, systolic). Factor VIII immunostains demonstrated that vascular density was significantly higher in the SC group than the C group. And % fibrosis and cell diameter were significantly lower in the SC group. And hematoxylin-eosin staining depicted that skeletal origin cells and well-developed-layered smooth muscle cells were detected in the implanted area. Positron emission tomography showed better myocardial perfusion and more viable myocardial tissue in the distressed myocardium receiving SC sheets compared with the myocardium receiving no sheets.
  
  
  CONCLUSIONS
  SC sheet implantation improved cardiac function by attenuating the cardiac remodeling in the porcine ischemic myocardium, suggesting a promising strategy for myocardial regeneration therapy in the impaired myocardium.
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Faculty of Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyagawa
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Saito
authors.forename: Taichi
authors.initials: T
authors.lastname: Sakaguchi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Imanishi
authors.forename: Naomasa
authors.initials: N
authors.lastname: Kawaguchi
authors.forename: Noboru
authors.initials: N
authors.lastname: Teramoto
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Iida
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shimizu
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
mesh_terms: D000758:Anesthesia / Q000379:methods / Q000662:veterinary; D000818:Animals; D003971:Diastole; D048091:Guided Tissue Regeneration / Q000379:methods*; D006321:Heart / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000502:physiology / Q000637:transplantation*; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D012038:Regeneration / Q000502:physiology*; D013318:Stroke Volume; D013552:Swine; D013599:Systole / Q000502:physiology; D023822:Tissue Engineering / Q000379:methods* / Q000639:trends; D014463:Ultrasonography