PROMOTION OF WOUND HEALING BY SF/HGF GENE THERAPY

描述（改编自申请人的摘要）：使用增长的承诺 改善慢性伤口愈合的因素尚未实现。基因 用编码生长因子基因的病毒载体治疗可能具有临床意义， 因为它可以延长伤口对细胞因子的暴露， 兴趣来自不同实验室的数据表明，分散因子/肝细胞 生长因子（SF/HGF），其诱导三种主要类型的细胞反应 体外（运动性、增殖和形态发生），改善伤口愈合 无论是在体外模型中还是在糖尿病动物中。本阶段的总体目标 我的项目是提供SF/HGF基因治疗增强血管生成的证据 正常、糖尿病和缺血皮肤的动物模型中的伤口愈合 伤口将通过三个具体目标实现这一目标：1）评估 重组人SF/HGF和含有重组人SF/HGF的腺病毒载体的作用 人SF/HGF（Ad5-SF/HGF）对伤口血管生成的作用的编码序列， 在猪皮肤切除伤口模型中的愈合; 2）比较效果 Ad5-SF/HGF对正常人与遗传性人伤口血管生成和愈合的影响 糖尿病小鼠（特别是，以证实未发表的报告，SF/HGF 显著改善糖尿病动物的伤口愈合，但不改善正常动物的伤口愈合）;以及 3)评估Ad5-SF/HGF对创伤愈合和血管生成的影响， 兔耳缺血创面模型。这些研究的结果将 为开发基因治疗的第二阶段项目提供基础， Ad5-SF/HGF用于临床应用。 拟定商业应用：不可用

DESCRIPTION (adapted from applicant's abstract): 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of Ad5-SF/HGF on wound angiogenesis and healing in normal vs. genetically diabetic mice (specifically, to confirm unpublished reports that SF/HGF significantly improves wound healing in diabetic, but not normal, animals); and 3) to evaluate the effect of Ad5-SF/HGF on wound healing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. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE