title: Myocardial transfection of hypoxia-inducible factor-1α and co-transplantation of mesenchymal stem cells enhance cardiac repair in rats with experimental myocardial infarction.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) have potential for the treatment of myocardial infarction. However, several meta-analyses revealed that the outcome of stem cell transplantation is dissatisfactory. A series of studies demonstrated that the combination of cell and gene therapy was a promising strategy to enhance therapeutic efficiency. The aim of this research is to investigate whether and how the combination of overexpression of hypoxia-inducible factor-1α (HIF-1α) and co-transplantation of mesenchymal stem cells can enhance cardiac repair in myocardial infarction.
  
  
  METHODS
  We investigated the therapeutic effects of myocardial transfection of HIF-1α and co-transplantation of MSCs on cardiac repair in myocardial infarction by using myocardial transfection of HIF-1α via an adenoviral vector. Myocardial infarction was produced by coronary ligation in Sprague-Dawley (SD) rats. Animals were divided randomly into six groups: (1) HIF-1α+MSCs group: Ad-HIF-1α (6×10⁹ plate forming unit) and MSCs (1×10⁶) were intramyocardially injected into the border zone simultaneously; (2) HIF-1α group: Ad-HIF-1α (6×10⁹ plate forming unit) was injected into the border zone; (3) HIF-1α-MSCs group: Ad-HIF-1α transfected MSCs (1×10⁶) were injected into the border zone; (4) MSCs group: MSCs (1×10⁶) were injected into the border zone; (5) CONTROL GROUP: same volume of DMEM was injected; (6) SHAM group. Cardiac performance was then quantified by echocardiography as well as molecular and pathologic analysis of heart samples in the peri-infarcted region and the infarcted region at serial time points. The survival and engraftment of transplanted MSCs were also assessed.
  
  
  RESULTS
  Myocardial transfection of HIF-1α combined with MSC transplantation in the peri-infarcted region improved cardiac function four weeks after myocardial infarction. Significant increases in vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α) expression, angiogenesis and MSC engraftment, as well as decreased cardiomyocyte apoptosis in peri-infarcted regions in the hearts of the HIF-1α+MSCs group were detected compared to the MSCs group and Control group.
  
  
  CONCLUSIONS
  These findings suggest that myocardial transfection of HIF-1α and co-transplantation of mesenchymal stem cells enhance cardiac repair in myocardial infarction, indicating the feasibility and preliminary safety of a combination of myocardial transfection of HIF-1α and MSC transplantation to treat myocardial infarction.
authors: Bingqing
authors: B
authors: Huang
authors: Juying
authors: J
authors: Qian
authors: Jianying
authors: J
authors: Ma
authors: Zheyong
authors: Z
authors: Huang
authors: Yunli
authors: Y
authors: Shen
authors: Xueying
authors: X
authors: Chen
authors: Aijun
authors: A
authors: Sun
authors: Junbo
authors: J
authors: Ge
authors: Haozhu
authors: H
authors: Chen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D015316:Genetic Therapy; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D009203:Myocardial Infarction / Q000235:genetics / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit