Lymphatic Regeneration within Porous VEGF-C Hydrogels for Secondary Lymphedema.

摘要

Lymphedema is an abnormal swelling in which lymph production exceeds drainage capabilities. This occurs as a result of lymphatic vessel destruction during the removal of lymph nodes or subsequent radiation therapy in breast cancer treatment. Management of lymphedema remains a clinical problem. In adult lymphangiogenesis, VEGF-C (Vascular Endothelium Growth Factor C) has been shown to be a specific mitogen for lymphatic endothelial cells (LEC) via the VEGF-C receptor. VEGF-C also has been shown to be required for proper lymphatic development via the Tie 2 receptor tyrosine kinase. In their model, the authors incorporated into alginate gel Angiopoietin-2 (Ang-2) and VEGF-C to promote lymphangiogenesis by stimulating LEC proliferation and migration. Sterile alginate gels with Ang-2 (2 micrograms/microliters) and VEGF-C (200 nanograms/microliters) were tested in vitro and in vivo for proliferation and migration. The results showed that by adding Ang-2 to the VEGF-C alginate gels, LEC proliferated and migration increased when compared to VEGF-C alginate gels. These gels also were compared in an in vivo mouse tail lymphedema model where they succeeded in reducing lymphedema and restoring lymphatic function in acute lymphedema animals. However, in chronic lymphedema animals, they were unable to induce the atrophic adipose tissue changes seen clinically in secondary lymphedema. Thus, the authors were unable to determine if this therapeutic application would have restored lymphatic function. The in vitro results demonstrate that alginate gels are an effective delivery system for Ang-2 and VEGF-C in the promotion of lymphangiogenesis. In the in vivo model, this therapy was successful for the acute lymphedema animals, but it was not successful for the chronic lymphedema animals. Further studies are required to evaluate this new therapy and its ability to restore lymphatic function in secondary chronic lymphedema in a different animal model.