title: Layered implantation of myoblast sheets attenuates adverse cardiac remodeling of the infarcted heart.
abstract: OBJECTIVE
  We previously showed that autologous myoblast sheets constructed with tissue-engineering techniques improved the function of the impaired heart. In this study, we evaluated the effects of layered myoblast sheets to clarify whether increasing the number of sheets provides improvement of cardiac function.
  
  
  METHODS
  Myoblast sheets were constructed in dishes that release confluent cells from the dish surface via temperature reduction. Sixty infarcted Lewis rats underwent implantation of myoblast sheets on the infarcted area. There were 4 groups (n = 15 in each group): S1: one layer, S3: three layers, S5: five layers, and a sham group. We examined cardiac function by echocardiography and catheterization, mRNA expression by real time reverse-transcriptase polymerase chain reaction, and histology.
  
  
  RESULTS
  The ejection fraction and end-systolic pressure-volume relationship in the S5 and S3 groups were significantly improved. End-diastolic area was significantly reduced in the S5 group. The mRNAs for hepatocyte growth factor, vascular endothelial growth factor, and stromal cell-derived factor-1 were all up-regulated in dose-dependent fashion. On histologic examination, fibrosis was most decreased in S5, and vascular density was increased. Cellular hypertrophy was attenuated in both the S5 and S3 groups. Elastic fibers were massively up-regulated in the infarction and implanted sheets in the S5 and S3 groups, with expression of the elastin gene.
  
  
  CONCLUSIONS
  Implantation of three- and five-layered myoblast sheets yields favorable results, with better improvement of cardiac function, induction of angiogenesis, more elastic fibers, and less fibrosis. Thus, layered myoblast sheets, in optimal numbers, may attenuate adverse cardiac remodeling of the infarcted heart.
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Naosumi
authors.initials: N
authors.lastname: Sekiya
authors.forename: Goro
authors.initials: G
authors.lastname: Matsumiya
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyagawa
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Saito
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shimizu
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
authors.forename: Naomasa
authors.initials: N
authors.lastname: Kawaguchi
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004452:Echocardiography; D004547:Elastic Tissue / Q000378:metabolism / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D032446:Myoblasts / Q000166:cytology / Q000637:transplantation*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D023822:Tissue Engineering; D014333:Tropoelastin / Q000378:metabolism; D016277:Ventricular Function, Left
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D014333:Tropoelastin