title: Engineered fetal cardiac graft preserves its cardiomyocyte proliferation within postinfarcted myocardium and sustains cardiac function.
abstract: The goal of cellular cardiomyoplasty is to replace damaged myocardium by healthy myocardium achieved by host myocardial regeneration and/or transplantation of donor cardiomyocytes (CMs). In the case of CM transplantation, studies suggest that immature CMs may be the optimal cell type to survive and functionally integrate into damaged myocardium. In the present study, we tested the hypothesis that active proliferation of immature CMs contributes graft survival and functional recovery of recipient myocardium. We constructed engineered cardiac tissue from gestational day 14 rat fetal cardiac cells (EFCT) or day 3 neonatal cardiac cells (ENCT). Culture day 7 EFCTs or ENCTs were implanted onto the postinfarct adult left ventricle (LV). CM proliferation rate of EFCT was significantly higher than that of ENCT at 3 days and 8 weeks after the graft implantation, whereas CM apoptosis rate remained the same in both groups. Echocardiogram showed that ENCT implantation sustained LV contraction, whereas EFCT implantation significantly increased the LV contraction at 8 weeks versus sham group (p < 0.05, analysis of variance). These results suggest that active CM proliferation may play a critical role in immature donor CM survival and the functional recovery of damaged recipient myocardium.
authors.affiliation: Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15224, USA.
authors.forename: Kazuro L
authors.initials: KL
authors.lastname: Fujimoto
authors.forename: Kelly C
authors.initials: KC
authors.lastname: Clause
authors.forename: Li J
authors.initials: LJ
authors.lastname: Liu
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Tinney
authors.forename: Shivam
authors.initials: S
authors.lastname: Verma
authors.forename: William R
authors.initials: WR
authors.lastname: Wagner
authors.forename: Bradley B
authors.initials: BB
authors.lastname: Keller
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Tobita
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D049109:Cell Proliferation; D005260:Female; D016332:Fetal Tissue Transplantation; D005333:Fetus / Q000166:cytology*; D006085:Graft Survival; D006321:Heart / Q000503:physiopathology*; D006334:Heart Function Tests; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology*; D018919:Neovascularization, Physiologic; D051381:Rats; D011917:Rats, Inbred Lew; D046509:Tissue Culture Techniques; D023822:Tissue Engineering / Q000379:methods*; D014463:Ultrasonography