Utilization of Vascular Endothelial Growth Factor-C156S in Therapeutic Lymphangiogenesis: A Systematic Review

Background: Vascular endothelial growth factor (VEGF) C156S is an engineering variant of VEGF-C that has the potential to promote lymphangiogenesis, activating on VEGF receptor (VEGFR) 3, without promoting angiogenesis (i.e., not acting on VEGFR-2). We conducted a systematic review of publications assessing the use of this growth factor in lymphedema treatment. We hypothesized that VEGF-C156S specificity for VEGFR-3 was an important differential for the lymphangiogenesis promoted by it. Methods and Results: We conducted a comprehensive systematic review of the published literature on PubMed/Medline, Embase, and Cochrane Clinical Answers. Eligibility criteria included articles reporting data on the use of VEGF-C156S in lymphedema treatment. We excluded articles that investigated physiology action of VEGF-C156S and articles that focused on other therapies. From 304 potential articles found in the literature, four studies fulfilled the study eligibility criteria. To date, all studies about this growth factor have been experimental. The effect of VEGF-C156 on lymph node transfer was investigated in half of the experiments. Interestingly, delivery of VEGF-C156S was mostly performed through viral gene transfer, but injection (subcutaneously or intravenously) of it as a protein (liposomal or nonliposomal) was also investigated by one author to assess drug bioavailability. Conclusions: Although authors reported promotion of lymphangiogenesis, VEGF-C156S was correlated with lymphatic hyperplasia or nonstatistically significant lymphangiogenesis compared with controls. Scientific evidence about the use of VEGF-C156S in lymphedema treatment is still limited. However, authors have shown that its lymphangiogenic effect is inferior to VEGF-C.