The effect of adipose-derived stem cells on ischemia-reperfusion injury: immunohistochemical and ultrastructural evaluation.
BACKGROUND
Advances in the treatment of reperfusion injury have created an opportunity for plastic surgeons to apply these treatments to flaps and implanted tissues. The authors examined the direct and indirect effects of adipose-derived stem cells on ischemia-reperfusion injury on a skin flap model to determine the in vivo differentiation of adipose-derived stem cells to endothelial cells; the levels of vascular endothelial growth factor (VEGF), transforming growth factor-beta, and fibroblast growth factor; and the ultrastructural changes apparent with scanning electron microscopy to clarify the initial events and the following cascades.


METHODS
Two identical cranial based random flaps with a dimension of 1 x 5 cm were elevated on the dorsums of 20 ICR mice. The left flap was designated as the control and the right flap was injected with adipose-derived stem cells. The flaps were then subjected to 6 hours of ischemia by clamping the pedicle, and then reperfusion.


RESULTS
The mean viable flap length in the control and experimental groups was 15.2 +/- 3.4 mm and 24.4 +/- 2.9 mm, respectively. The mean viable flap area in the control and experimental groups was 12.9 +/- 4.1 mm and 21.8 +/- 3.7 mm, respectively. The in vivo differentiation of adipose-derived stem cells to endothelial cells was observed. The immunohistochemical stainings, VEGF, transforming growth factor-beta, and fibroblast growth factor revealed increased levels in the experimental groups. Scanning electron microscopy indicated mild injury in the experimental group.


CONCLUSIONS
The adipose-derived stem cells could prevent ischemia-reperfusion injury, mainly by regulating the growth factors. Although VEGF was the foremost inhibitor of injury, the overall cascade was enhanced by adipose-derived stem cells, with the help of the other growth factors.
Uysal
A Cagri
AC
Tokyo, Japan From the Department of Plastic and Reconstructive Surgery, Nippon Medical School.
Mizuno
Hiroshi
H
Tobita
Morikuni
M
Ogawa
Rei
R
Hyakusoku
Hiko
H
D017667:Adipocytes; D000792:Angiography; D000818:Animals; D002454:Cell Differentiation; D005346:Fibroblast Growth Factors / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008813:Mice, Inbred ICR; D008852:Microradiography; D018919:Neovascularization, Physiologic; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D013524:Surgical Flaps / Q000098:blood supply* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors