Therapeutic lymphangiogenesis using stem cell and VEGF-C hydrogel

Biomaterials. 2011 Jul;32(19):4415-23. doi: 10.1016/j.biomaterials.2011.02.051. Epub 2011 Mar 21.

Abstract

Lymphedema is a manifestation of lymphatic system insufficiency. It arises from primary lymphatic dysplasia or secondary obliteration after lymph node dissection or irradiation. Although improvement of swelling can be achieved by comprehensive non-operative therapy, treatment of this condition requires lifelong care and good compliance. Recently molecular-based treatments using VEGF-C have been investigated by several researchers. We designed the present study to determine whether the therapeutic efficacy of implanted human adipose-derived stem cells (hADSCs) could be improved by applying a gelatin hydrogel containing VEGF-C (VEGF-C hydrogel) to the site of tissue injury in a lymphedema mouse model. Four weeks after the operation, we evaluated edema and determined lymphatic vessel density at various post-operative time points. Mice treated with hADSCs and VEGF-C hydrogel showed a significantly decreased dermal edema depth compared to the groups of mice that received hADSCs only or VEGF-C hydrogel only. Immunohistochemical analysis also revealed that the hADSC/VEGF-C hydrogel group showed significantly greater lymphatic vessel regeneration than all the other groups. hADSCs were detected in the implantation sites of all mice in the hADSC/VEGF-C group, and exhibited a lymphatic endothelial differentiation phenotype as determined by co-staining PKH-labeled hADSCs for the lymphatic marker LYVE-1. Our results suggest that co-administration of hADSCs and VEGF-C hydrogel has a substantial positive effect on lymphangiogenesis.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / metabolism
  • Biocompatible Materials / therapeutic use
  • Disease Models, Animal
  • Female
  • Gelatin / chemistry
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry
  • Hydrogel, Polyethylene Glycol Dimethacrylate / pharmacology*
  • Lymphangiogenesis*
  • Lymphedema / therapy*
  • Materials Testing
  • Mice
  • Mice, Inbred BALB C
  • Regeneration / physiology
  • Stem Cell Transplantation*
  • Stem Cells / cytology
  • Stem Cells / physiology*
  • Vascular Endothelial Growth Factor C / pharmacology*

Substances

  • Biocompatible Materials
  • Vascular Endothelial Growth Factor C
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Gelatin