sFlt-1 gene-transfected fibroblasts: A wound-specific gene therapy inhibits local cancer recurrence

Local recurrence occurs frequently at the site of injury after surgical res ection. On the other hand, fibroblasts have been shown to accumulate in the injured area to heal and remodel the damaged tissues. Therefore, fibroblas ts are likely to be useful as wound-specific vectors for delivery of genes to sites of surgically injury. The present study was performed to investiga te wound-specific migration of exogenously administered fibroblasts and eff icacy of gene therapy using genetically engineered fibroblasts in an i.p. w ound recurrence model in rats. We demonstrated that fibroblasts transfected with the GFP gene accumulated specifically around the site of injury immed iately after i.p. injection. Then, fibroblasts transfected with an adenovir us designated as AdFex that encoded the soluble form of Flt-1 (sFlt-1), a v ascular endothelial growth factor receptor, were administered i.p. to the r ats to examine inhibition of tumor growth. At day 16 after implantation, a significantly smaller tumor volume and less microvessel density in wound si tes were observed in the AdFex/fibroblast-treated rats than in controls. Fu rthermore, this treatment also resulted in an improved survival rate. In co nclusion, autologous fibroblasts show promise as a wound-specific vector fo r gene therapy, and administration of sFlt-1 gene-engineered fibroblasts co ntributed to local control of the tumor around the injured tissue.