Adipose-derived stem cell transplantation for therapeutic lymphangiogenesis in a mouse secondary lymphedema model

Regen Med. 2015;10(5):549-62. doi: 10.2217/rme.15.24.

Abstract

Aim: Secondary lymphedema is observed in common after postmalignancy treatment of the breast and the gynecologic organs but effective therapies are not established. Adipose-derived stem cells (ADSCs), which are pluripotent, regenerative in local injection, are tested for murine hindlimb secondary lymphedema by regenerative method.

Methods & results: Mice were divided into four groups: no ADSCs, 1 × 10(6) ADSCs, 1 × 10(5) ADSCs and 1 × 10(4) ADSCs (each group, n = 20) in a stringent surgical resection and irradiation. Circumferential measurement, lymphatic flow assessment and quantification of lymphatic vessels were performed.

Results: The numbers of lymphatic vessels by LYVE-1 immunohistochemistry, and VEGF-C- or VEGFR3-expressing cells were significantly increased in transplanted groups (p < 0.05).

Conclusion: ADSCs can restore the lymphatic vascular network in secondary lymphedema with increased collecting vessels.

Keywords: VEGF-C; VEGFR3; adipose-derived stem cell; lymphangiogenesis; mouse; radiation; secondary lymphedema; surgery.

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Disease Models, Animal
  • Female
  • Glycoproteins / metabolism
  • Green Fluorescent Proteins / metabolism
  • Hindlimb / pathology
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Infrared Rays
  • Lymphangiogenesis / physiology*
  • Lymphatic Vessels / metabolism
  • Lymphedema / therapy*
  • Male
  • Membrane Transport Proteins
  • Mice
  • Mice, Inbred C57BL
  • Regeneration
  • Stem Cell Transplantation*
  • Vascular Endothelial Growth Factor C / metabolism
  • Vascular Endothelial Growth Factor Receptor-3 / metabolism
  • Video Recording

Substances

  • Glycoproteins
  • Membrane Transport Proteins
  • Vascular Endothelial Growth Factor C
  • Xlkd1 protein, mouse
  • Green Fluorescent Proteins
  • Vascular Endothelial Growth Factor Receptor-3