Adenovirus-mediated ex vivo gene transfer of human vascular endothelial growth factor in a rabbit laryngotracheal reconstruction model

Free autologous cartilage, which is used in laryngotracheal reconstruction (LTR), may undergo progressive necrosis as a result of delayed revascularization. Angiogenic growth factors, such as vascular endothelial growth factor (VEGF), promote angiogenesis in the ischemic environment. We studied the effect of ex vivo gene transfer of VEGF(121) on cartilage angiogenesis and graft survival in a rabbit model of LTR. Sixty rabbits underwent LTR with auricular cartilage. The grafts were treated at 1 x 10(9) plaque-forming units with 1) VEGF(121) (n = 20), 2) LacZ reporter gene (n = 20), or 3) saline solution (n = 20). Graft neovascularization and survival were histologically assayed at 1 and 10 weeks. Angiogenesis was enhanced at both 1 and 10 weeks after treatment with VEGF(121) as compared to controls (p < .001). No statistical improvement in graft survival was evident after treatment with VEGF(121). Ex vivo gene transfer to cartilage may be a promising gene therapy strategy to enhance revascularization - and, potentially, cartilage survival - under the proper conditions.