Effect of vascular endothelial growth factor C (VEGF-C) gene transfer in rat model of secondary lymphedema

Secondary lymphedema has been clinically well described, but a cure is still lacking. Although there have been previous investigations using plasmid DNA for gene therapy, few have focused on the use for the treatment of lymphedema. Therefore, we investigated the effects of VEGF-C gene transfer for the treatment of lymphedema using our plasmid pcDNA3.1-VEGF-C. We produced a surgical model of secondary lymphedema in the rat hindlimb and treated with local intradermal VEGF-C transfection to investigate the efficacy of gene transfer. Magnetic resonance imaging (MRI) (P < 0.05), B ultrasound (P < 0.05), and water displacement volumetry (P < 0.05) demonstrated a reduction of lymphedema in therapy group as compared to controls. Histological and immunofluorescent studies demonstrated numerous newly formed lymphatic vessels in therapy group. Our results indicate that VEGF-C gene therapy has produced new lymphatic vessels which may have improved functional lymphatic drainage to reduce lymphedema volume in our model.