title: Effects of hepatocyte growth factor overexpressed bone marrow-derived mesenchymal stem cells on prevention from left ventricular remodelling and functional improvement in infarcted rat hearts.
abstract: Bone marrow-derived mesenchymal stem cells (BM-MSCs ) transplantation has been reported to be a promising therapy for myocardial infarction (MI). However, low survival rate of BM-MSCs in infarcted heart is one of the major limitations for the perspective clinical application. In this study, we aimed to investigate the effect of hepatocyte growth factor (HGF) on left ventricular function improvement of HGF gene-modified BM-MSCs (HGF-MSCs) after its delivery into the infarcted rat hearts. BM-MSCs were isolated with fibroblast-like morphology and expressed CD44+CD29+CD90+/CD34-CD45-CD31-CD11a. After 5-azacytidine induction in vitro, 20%-30% of the cells were positively stained for desmin, cardiac-specific cardiac troponin I and connexin-43. Histological staining revealed that 2 weeks after MI is an optimal time point with decreased neutrophil infiltration and increased vascular number. Minimal infarct size and best haemodynamic analysis were also observed after cell injection at 2 weeks compared with that of 1 h, 1 week or 4 weeks. Echocardiogram confirmed that transplantation with HGF-MSCs significantly improved left ventricular function compared with other groups in rat MI models. MSCs and HGF-MSCslabelled with DAPI were detected 4 weeks after MI in the infarcted area. Decreased infarcted scar area and increased angiogenesis formation could be found in HGF-MSCs group than in other groups as demonstrated by hematoxylin and eosin (H&E) staining and factor VIII staining. These results indicate that HGF-MSCs transplantation could enhance the contractile function and attenuate left ventricular remodelling efficiently in rats with MI.
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Shenxu
authors.initials: S
authors.lastname: Wang
authors.forename: Xing
authors.initials: X
authors.lastname: Qin
authors.forename: Dongdong
authors.initials: D
authors.lastname: Sun
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xie
authors.forename: Weiwei
authors.initials: W
authors.lastname: Fan
authors.forename: Yabin
authors.initials: Y
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Liang
authors.forename: Xuetao
authors.initials: X
authors.lastname: Pei
authors.forename: Feng
authors.initials: F
authors.lastname: Cao
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology*; D002478:Cells, Cultured; D003331:Coronary Vessels; D004195:Disease Models, Animal; D005260:Female; D006439:Hemodynamics; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000628:therapy; D018919:Neovascularization, Physiologic; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection; D020257:Ventricular Remodeling
chemical_list: D017228:Hepatocyte Growth Factor; D001374:Azacitidine