Extracorporeal shock wave therapy combined with vascular endothelial growth factor-C hydrogel for lymphangiogenesis

J Vasc Res. 2013;50(2):124-33. doi: 10.1159/000343699. Epub 2012 Nov 27.

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/mm(2), 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Combined Modality Therapy
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Drug Implants
  • Female
  • Gelatin
  • Gene Expression Regulation / drug effects
  • High-Energy Shock Waves / therapeutic use*
  • Hindlimb
  • Hydrogels
  • Lymphangiogenesis / drug effects*
  • Lymphatic Vessels / drug effects
  • Lymphatic Vessels / injuries
  • Lymphatic Vessels / physiology
  • Lymphedema / drug therapy
  • Lymphedema / therapy*
  • Macrophage Activation / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Regeneration / drug effects
  • Vascular Endothelial Growth Factor C / administration & dosage
  • Vascular Endothelial Growth Factor C / biosynthesis
  • Vascular Endothelial Growth Factor C / genetics
  • Vascular Endothelial Growth Factor C / therapeutic use*
  • Vascular Endothelial Growth Factor Receptor-3 / biosynthesis
  • Vascular Endothelial Growth Factor Receptor-3 / genetics
  • Wound Healing / drug effects
  • Wound Healing / physiology

Substances

  • Drug Implants
  • Hydrogels
  • Vascular Endothelial Growth Factor C
  • vascular endothelial growth factor C, mouse
  • Gelatin
  • Vascular Endothelial Growth Factor Receptor-3