Tissue edema and secondary lymphedema are common problems in surgery. Discovery of the first lymphangiogenic growth factors now allow us to develop new targeted therapies for lymphedema. The vascular endothelial growth factor-C and -D are the first known growth factors that are capable of inducing growth of new lymphatic vessels. The authors have recently shown that insufficient signaling of VEGF-C/D causes hereditary lymphedema in some families and VEGF-C therapy shows promising effects in preclinical animal models of lymphedema).
Now they have used VEGF-C gene therapy to regenerate the collecting lymphatic vessels after surgical removal of the axillary lymph nodes in a mouse model. Gene transfer vectors encoding either VEGF-C or LacZ control genes (5 × 108 pfu) were injected into tissues surrounding the site of lymph node dissection. Lymphatic flow in and around the axillary region was analyzed 1, 2, 10 weeks or 6 months after the operation by fluorescent microlymphangiography. Their unpublished results showed that VEGF-C gene transfer is able to induce growth of collecting lymphatic vessels in the axilla. In the LacZ treated control animals, collecting lymphatic vessels are missing after operation.
Of interest, nonfunctional lymphatic vessels seem to regress when the adenoviral VEGF-C gene expression is downregulated 2 weeks after operation, but functional collecting vessels are detected in the axilla even 6 months after operation. Immunohistochemical analysis reveals that these new collecting lymphatic vessel align the pre-existing blood vessels. The authors envision that VEGF-C therapy could be used in the treatment of lymphedema and also in reconstructive surgery to reduce edema and thereby to improve perfusion in the operated tissues.
