Extracorporeal Shock Wave Therapy Combined with Vascular Endothelial Growth Factor-C Hydrogel for Lymphangiogenesis

Abstract

Background/Aims: Lymphedema is a clinically incurable disease that occurs commonly after lymph node dissection and/or irradiation. Several studies have recently demonstrated that extracorporeal shock wave therapy (ESWT) could promote lymphangiogenesis associated with expression of vascular endothelial growth factor (VEGF)-C. This research concerned primarily the synergistic effect of ESWT combined with VEGF-C incorporated hydrogel (VEGF-C hydrogel) combination therapy for promoting lymphangiogenesis and ultimately alleviating lymphedema. Methods: The VEGF-C hydrogel was applied to the injury site in a mouse model of lymphedema and then regularly underwent ESWT (0.05 mJ/mm², 500 shots) every 3 days for 4 weeks. Results: Four weeks after the treatment, mice treated with VEGF-C hydrogel and ESWT showed signs of the greatest decrease in edema/collagenous deposits when compared with the other experimental group. LYVE-1-positive vessels also revealed that the VEGF-C/ESWT group had significantly induced the growth of new lymphatic vessels compared to the other groups. Western blot analysis showed that expression of VEGF-C (1.24-fold) and VEGF receptor-3 (1.41-fold) was significantly increased in the VEGF-C/ESWT group compared to the normal group. Conclusion: These results suggested that VEGF-C and ESWT had a synergistic effect and were very effective in alleviating the symptoms of lymphedema and promoting lymphangiogenesis.