Effect of fibrin matrix and vascular endothelial growth factor on reepithelialization of orthotopic murine tracheal transplants

To determine whether the administration of vascular endothelial growth factor (VEGF) alone and in combination with fibrin matrix accelerates murine tracheal allograft reepithelialization, we randomly assigned 40 age-matched mice to 5 experimental groups. BALB/c tracheal grafts were transplanted orthotopically into allogeneic C57BL/6 recipients. The recipients were immunosuppressed with cyclosporine (25 mg/kg per day) and treated with a single topical dose of fibrin matrix, a single topical dose of VEGF, or a single topical dose of a combination of VEGF and fibrin matrix. Thirty-five and 50 days after transplantation, a mixed lymphocyte reaction was performed to assess adequate immunosuppression and the grafts were assessed for rejection, rate and quality of allograft reepithelialization, and cartilage viability. The administration of a combination of fibrin matrix and VEGF to tracheal allografts demonstrated an increased rate of reepithelialization and increased density (37% ± 2.9%) of morphologically normal ciliated pseudostratified epithelium when compared with an immunosuppressed control group (29.3% ± 9.1%) 35 days after transplantation. The treated allografts demonstrated no significant change in cartilage viability or rejection. We conclude that the administration of fibrin matrix and VEGF to immunosuppressed tracheal allografts improves the rate and density of tracheal allograft reepithelialization. Carrier-bound growth factors may represent a novel approach to accelerating tracheal allograft reepithelialization and decreasing the need for prolonged immunosuppression following tracheal transplantation.