Wound Healing and Angiogenesis through Combined Use of a Vascularized Tissue Flap and Adipose-Derived Stem Cells in a Rat Hindlimb Irradiated Ischemia Model

Plast Reconstr Surg. 2016 May;137(5):1486-1497. doi: 10.1097/PRS.0000000000002062.

Abstract

Background: Treatment of critical limb ischemia is sometimes difficult because of the patient's condition, and some novel approaches are needed.

Methods: The hindlimbs of Sprague-Dawley rats, after 20-Gy x-ray irradiation and surgical occlusion, were divided into four groups: with a superficial fascial flap, 5.0 × 10 adipose-derived stromal/stem cells, and both combined. The rats were tested for laser tissue blood flow, immunohistologic blood vessel density, and foot paw punch hole wound healing. Green fluorescent protein-tagged Sprague-Dawley rats were used for further investigation by cell tracking for 2 weeks.

Results: Laser tissue blood flow demonstrated a significant increase in the combined treatment of flap and adipose-derived stem cells at both 1 and 2 weeks. There were no significant differences between the treatment groups treated with flaps alone and those treated with adipose-derived stem cells alone. Wound healing was significantly increased following combined treatment at 1 week, and there was no wound by 2 weeks except for the no-flap and no-adipose-derived stem cell group. The number of vessels depicted by von Willebrand factor showed a significant increase in the combined treatment group, at both 1 week and 2 weeks. In the cell tracking group, at 2 weeks, the green fluorescent protein-tagged adipose-derived stem cells were significantly more positive in the no-flap group than in the flap group.

Conclusions: Adipose-derived stem cells may be a potent cell source in irradiated and occluded limbs by enhancing tissue blood flow and blood vessel density. Adipose-derived stem cells may play an important role in some difficult ischemic conditions in terms of wound healing.

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Green Fluorescent Proteins / analysis
  • Hindlimb / blood supply
  • Hindlimb / radiation effects
  • Ischemia / surgery*
  • Ischemia / therapy
  • Male
  • Neovascularization, Physiologic*
  • Radiation Injuries, Experimental / surgery
  • Radiation Injuries, Experimental / therapy
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Transgenic
  • Stem Cell Transplantation*
  • Surgical Flaps* / blood supply
  • Wound Healing*
  • von Willebrand Factor / analysis

Substances

  • von Willebrand Factor
  • Green Fluorescent Proteins