Wound Healing and Angiogenesis through Combined Use of a Vascularized Tissue Flap and Adipose-Derived Stem Cells in a Rat Hindlimb Irradiated Ischemia Model.
Treatment of critical limb ischemia is sometimes difficult because of the patient's condition, and some novel approaches are needed.



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.



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.



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.
Nagasaki, Japan.|From the Department of Plastic and Reconstructive Surgery, Nagasaki University Hospital.
Shuhei
S
Yoshida
Nagasaki, Japan.|From the Department of Plastic and Reconstructive Surgery, Nagasaki University Hospital.
Hiroshi
H
Yoshimoto
Nagasaki, Japan.|From the Department of Plastic and Reconstructive Surgery, Nagasaki University Hospital.
Akiyoshi
A
Hirano
Nagasaki, Japan.|From the Department of Plastic and Reconstructive Surgery, Nagasaki University Hospital.
Sadanori
S
Akita
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D049452:Green Fluorescent Proteins / Q000032:analysis; D006614:Hindlimb / Q000098:blood supply / Q000528:radiation effects; D007511:Ischemia / Q000601:surgery* / Q000628:therapy; D008297:Male; D018919:Neovascularization, Physiologic; D011833:Radiation Injuries, Experimental / Q000601:surgery / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D033581:Stem Cell Transplantation; D013524:Surgical Flaps / Q000098:blood supply; D014945:Wound Healing; D014841:von Willebrand Factor / Q000032:analysis
D014841:von Willebrand Factor; D049452:Green Fluorescent Proteins