title: Wnt1-overexpressing skeletal myoblasts as an improved cell therapy for cardiac repair following myocardial infarction.
abstract: OBJECTIVE
  Recent findings highlight the critical role of the Wnt signaling pathway in cardiac repair and stem cell regulation. Our previous study shows that lithium chloride (LiCl) optimizes skeletal myoblast (SkM) for transplantation by mimicking the Wnt/β-catenin signaling activities. In this study, we evaluate the therapeutic potential of SkMs genetically modified with Wnt1gene (Wnt1 SkMs) in a rat model with myocardial infarction (MI).
  
  
  METHODS
  We harvested neonatal SkMs using Wistar rats (1-3-day old) transfected with p-EGFP-C3-Wnt1 plasmid. RT-PCR and immunofluorescence showed a higher expression of Wnt1 in the Wnt1 SkMs. We observed that Wnt1 SkMs increased connexin 43 (Cx43) expression, reduced apoptosis induced by hydrogen peroxide (H2O2) and decreased caspase-3 expression via the canonical Wnt signaling pathways compared to the empty vector transfected SkMs (control SkMs). For in vivo studies, the myocardial infarction model was developed in the Wistar rats. The rats were grouped to receive 100 μL basal DMEM without cells or containing 1.5×106SkMs and Wnt1 SkMs. Histological studies revealed improved survival of SkMs, reduced cardiomyocytes apoptosis, and upregulated expression of Cx43 in Wnt1 SkMs therapy group. Echocardiography monitored four weeks after therapy showed improvement of the left ventricular function in rats treated with Wnt1SkMs compared to other groups.
  
  
  CONCLUSIONS
  Transplantation of Wnt1 SkMs improves rat myocardial function and enhances anti apoptotic properties of both SkMs and cardiomyocytes and upregulation of tissue Cx43 after infarction via the canonical Wnt/β-catenin signaling activities.
authors.affiliation: The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education - qi33345@163.com.
authors.forename: G Q
authors.initials: GQ
authors.lastname: Du
authors.forename: W J
authors.initials: WJ
authors.lastname: Du
authors.forename: J J
authors.initials: JJ
authors.lastname: Liu
authors.forename: Y S
authors.initials: YS
authors.lastname: Wang
authors.forename: H G
authors.initials: HG
authors.lastname: Nie
authors.forename: M M
authors.initials: MM
authors.lastname: Zhang
authors.forename: B
authors.initials: B
authors.lastname: Yu
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D051155:Wnt1 Protein / Q000378:metabolism*
chemical_list: D018031:Connexin 43; C580592:Gja1 protein, rat; D051155:Wnt1 Protein; C495245:Wnt1 protein, rat