Myocardial transfection of hypoxia-inducible factor-1? and co-transplantation of mesenchymal stem cells enhance cardiac repair in rats with experimental myocardial infarction.

ABSTRACT: INTRODUCTION: 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-1? (HIF-1?) 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-1? and co-transplantation of MSCs on cardiac repair in myocardial infarction by using myocardial transfection of HIF-1? 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-1?+MSCs group: Ad-HIF-1? (6×10? plate forming unit) and MSCs (1×10?) were intramyocardially injected into the border zone simultaneously; (2) HIF-1? group: Ad-HIF-1? (6×10? plate forming unit) was injected into the border zone; (3) HIF-1?-MSCs group: Ad-HIF-1? transfected MSCs (1×10?) were injected into the border zone; (4) MSCs group: MSCs (1×10?) 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-1? 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-1? (SDF-1?) expression, angiogenesis and MSC engraftment, as well as decreased cardiomyocyte apoptosis in peri-infarcted regions in the hearts of the HIF-1?+MSCs group were detected compared to the MSCs group and Control group. CONCLUSIONS: These findings suggest that myocardial transfection of HIF-1? 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-1? and MSC transplantation to treat myocardial infarction.

SUBMITTER: Huang B 

PROVIDER: S-EPMC4055118 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature