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The Effect of Human Adipose-Derived Stem Cells on Healing of Ischemic Wounds in a Diabetic Nude Mouse Model

Kim, Eun Key M.D., Ph.D.; Li, Guang M.D.; Lee, Taik Jong M.D., Ph.D.; Hong, Joon Pio M.D., Ph.D.

Plastic and Reconstructive Surgery: August 2011 - Volume 128 - Issue 2 - p 387-394
doi: 10.1097/PRS.0b013e31821e6de2
Experimental: Original Articles

Background: Among hundreds of pathophysiologic factors that impair healing of the diabetic foot, diminished perfusion and neovascularization are critical. This study aimed to show the effect of human adipose-derived stem cells on healing of ischemic wounds in diabetic nude mice and thus to estimate the possibilities of adipose-derived stem cells for diabetic wound care.

Methods: Sixty nude mice were assigned randomly into group Ia (diabetic control, n = 20), group Ib (diabetic experimental, n = 20), or group II (nondiabetic control, n = 20). After creation of an ischemic limb, human adipose-derived stem cells were injected locally. Gross and histologic observations were made after 3, 7, and 25 days, and plasma and tissue levels of vascular endothelial growth factor were quantified.

Results: Group Ia animals typically showed gangrene formation with a delayed and sustained inflammatory reaction, which led to a high rate of autoamputation and a lower survival rate. Group Ib animals had a tendency for earlier and abundant neovessel formation and better tissue remodeling rather than fibrotic cicatrization, resulting in lower rate of autoamputation and a survival rate comparable to group II. Surviving stem cells were identified at day 25, but no specific differentiation was observed. Plasma and tissue vascular endothelial growth factor level in group Ib was higher than in group Ia and comparable to that in group II.

Conclusions: This study demonstrated the beneficial effect of human adipose-derived stem cells on healing of ischemic wound in diabetic nude mice. Elevation of vascular endothelial growth factor levels in plasma and tissue suggests the importance of secretory factor, which regulates local angiogenesis and triggers a systemic response.

Seoul, Korea

From the Department of Plastic Surgery, Asan Medical Center, and the Laboratory of Immunology and Transplantation, Asan Institute for Life Science, University of Ulsan College of Medicine.

Received for publication April 14, 2010; accepted February 18, 2011.

Disclosure: The authors have no financial interest in any of the products or devices mentioned in this article.

Eun Key Kim, M.D., Ph.D., Department of Plastic Surgery, Asan Medical Center, Songpa-gu, Poongnap2-dong, 388-1, Seoul 138-736, Korea,

©2011American Society of Plastic Surgeons