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 VEGF121 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) VEGF121 (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 VEGF121 as compared to controls (p < .001). No statistical improvement in graft survival was evident after treatment with VEGF121. Ex vivo gene transfer to cartilage may be a promising gene therapy strategy to enhance revascularization--and, potentially, cartilage survival--under the proper conditions.
Samadi
Daniel S
DS
Division of Pediatric Otolaryngology, The Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
Jacobs
Ian N
IN
Walsh
Danielle
D
Bouchard
Sarah
S
Herlyn
Meenhard
M
Crombleholme
Timothy M
TM
D000256:Adenoviridae / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D004425:Ear Cartilage / Q000473:pathology / Q000637:transplantation*; D016228:Endothelial Growth Factors / Q000235:genetics*; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors; D006085:Graft Survival; D006801:Humans; D007150:Immunohistochemistry; D007763:Lac Operon; D007830:Larynx / Q000601:surgery*; D008222:Lymphokines / Q000235:genetics*; D009336:Necrosis; D018919:Neovascularization, Physiologic; D011817:Rabbits; D019651:Plastic Surgery Procedures; D013997:Time Factors; D014132:Trachea / Q000601:surgery*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors