title: Transplantation of novel vascular endothelial growth factor gene delivery system manipulated skeletal myoblasts promote myocardial repair.
abstract: BACKGROUND
  Skeletal myoblast (SkM) transplantation combined with vascular endothelial growth factor (VEGF) gene delivery has been proposed as a promising therapy for cardiac repair. Nevertheless, the defective gene vectors and unregulable VEGF expression in vivo hinder its application. Therefore, the search for an economical, effective, controllable gene delivery system is quite necessary.
  
  
  METHODS
  In our study, hyperbranched polyamidoamine (h-PAMAM) dendrimer was synthesized as a novel gene delivery vector using a modified method. And hypoxia-regulated human VEGF-165 plasmids (pHRE-hVEGF165) were constructed for controllable VEGF gene expression. The efficiency and feasibility of h-PAMAM-HRE-hVEGF165 gene delivery system manipulated SkM transplantation for cardiac repair were investigated in myocardial infarction models.
  
  
  RESULTS
  The h-PAMAM encapsulated pHRE-hVEGF165 could resist nuclease digestion for over 120 min. In primary SkMs, h-PAMAM-pHRE-hVEGF165 gene delivery system showed high transfection efficiency (43.47 ± 2.22%) and minor cytotoxicity (cell viability = 91.38 ± 0.48%). And the transfected SkMs could express hVEGF165 for 18 days under hypoxia in vitro. For myocardial infarction models, intramyocardial transplantation of the transfected SkMs could result in reduction of apoptotic myocardiocytes, improvement of grafted cell survival, decrease of infarct size and interstitial fibrosis, and increase of blood vessel density, which inhibited left ventricle remodeling and improved heart function at the late phase following infarction.
  
  
  CONCLUSIONS
  These results indicate that h-PAMAM based pHRE-hVEGF165 gene delivery into SkMs is feasible and effective, and may serve as a novel and promising gene therapy strategy in ischemic heart disease.
authors.affiliation: Department of Cardiac Surgery, Zhongshan Hospital, Fudan University & Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhu
authors.forename: Changfa
authors.initials: C
authors.lastname: Guo
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.forename: Hao
authors.initials: H
authors.lastname: Lai
authors.forename: Wuli
authors.initials: W
authors.lastname: Yang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Dongli
authors.initials: D
authors.lastname: Song
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D009203:Myocardial Infarction / Q000235:genetics* / Q000601:surgery*; D011073:Polyamines; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C531249:Poly(amidoamine); D011073:Polyamines; D042461:Vascular Endothelial Growth Factor A
keywords: Cardiac repair; Hyperbranched polyamidoamine; Hypoxia; Skeletal myoblast; Vascular endothelial growth factor