Vascular endothelial growth factor-C gene therapy restores lymphatic flow across incision wounds

SPECIFIC AIMSLymphatic insufficiency, edema, and poor blood perfusion are common problems in reconstructive surgery. We aimed at rebuilding the lymphatic vessel network severed after surgical incision by introducing adenoviral vascular endothelial growth factor C (VEGF-C) gene transfer to the edges of a cutaneous flap. The feasibility of this form of therapy was assessed by assaying drainage of lymphatic fluid from the flap to axillary lymph nodes across the incision wound, and by quantification of lymphatic vessels in the wound area.PRINCIPAL FINDINGS1. Adenoviral VEGF-C and VEGF-C156S restore drainage of lymphatic fluid across the incision woundLymphatic vessel function is lost after surgical incision. VEGF-C is the first growth factor that was found capable of directly inducing growth of new lymphatic vessels via VEGFR-3, the principal mediator of lymphangiogenic signals. In this study, we have used adenoviral gene transfer of VEGF-C or VEGF-C156S, a mutant ligand specific for VEGFR-3, in an epigastric...