The promise of using growth factors to improve healing of chronic wounds has not yet been realized. Gene therapy with viral vectors coding for growth factor genes may have clinical utility because it could prolong exposure of wounds to the cytokine of interest. Data from various laboratories suggest that scatter factor/hepatocyte growth factor (SF/HGF), which induces three major classes of cellular responses in vitro (motility, proliferation, and morphogenesis), improves wound healing both in in vitro models and in diabetic animals. The overall goal of this phase I project is to produce evidence that SF/HGF gene therapy enhances angiogenesis and/or wound healing in animals models of normal, diabetic, and ischemic dermal wounds. This goal will be pursued through three specific aims: 1) to evaluate the effects of recombinant human SF/HGF and an adenoviral vector containing the coding sequences for human SF/HGF (Ad5-SF/HGF) on wound angiogenesis and healing in the porcine excisional dermal wound model; 2) to compare the effects of Ad5-SF/HGF on wound angiogenesis and healing in normal vs. genetically diabetic mice (specifically, to confirm unpublished reports that SF/HGF significantly improves wound healing in diabetic, but not normal, animals); and 3) to evaluate the effect of Ad5-SF/HGF on wound healing and angiogenesis in the rabbit ear ischemic wound model. The results from these studies will provide the basis for a phase II project to develop gene therapy with Ad5-SF/HGF for clinical applications.
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