A highly infectious chimeric adenovirus expressing basic fibroblast growth factor exerts potent targeted therapy for rabbit ear chronic ischemic wounds.

Abstract

Poor angiogenesis and impaired proliferation of cells responsible for the repair of chronic ischemic wounds result in impaired wound healing. The continuous and efficient expression of therapeutic factors by means of gene transfection is an ideal adjuvant treatment method to promote cell proliferation and angiogenesis. A chimeric recombinant adenoviral vector, Ad5F35ET1-bFGF, was constructed that carried the basic fibroblast growth factor (bFGF) gene and used the endothelin-1 promoter to control the targeted expression of bFGF in endothelial cells and fibroblasts. Thus, the authors established a targeted gene therapy for chronic ischemic wounds. The chimeric adenovirus Ad5F35ET1-bFGF efficiently infected the endothelin-1-positive endothelial cells and fibroblasts, specifically expressed bFGF, and promoted cell proliferation. In the rabbit wound healing model, the chimeric recombinant adenovirus expressed a high level of bFGF in wound tissues, which continuously promoted angiogenesis and cell proliferation and thus accelerated wound healing. Targeted gene therapy that uses bFGF as a therapeutic gene provides an effective candidate strategy for the treatment of chronic ischemic wounds.