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Bone Marrow–Derived Mesenchymal Stem Cells Enhanced Diabetic Wound Healing through Recruitment of Tissue Regeneration in a Rat Model of Streptozotocin-Induced Diabetes

Kuo, Yur-Ren M.D., Ph.D.; Wang, Chun-Ting B.S.; Cheng, Jiin-Tsuey Ph.D.; Wang, Feng-Sheng Ph.D.; Chiang, Yuan-Cheng M.D.; Wang, Ching-Jen M.D.

Plastic & Reconstructive Surgery: October 2011 - Volume 128 - Issue 4 - p 872–880
doi: 10.1097/PRS.0b013e3182174329
Experimental: Original Articles

Background: This study investigated whether bone marrow–derived mesenchymal stem cell therapy has effectiveness in the enhancement of diabetic wound healing through tissue regeneration.

Methods: The authors used a dorsal skin defect (6 × 5 cm) in a streptozotocin-induced diabetes rodent model. Forty male Wistar rats were divided into four groups: group I, nondiabetic rats (controls); group II, diabetic controls receiving no mesenchymal stem cells; group III, rats receiving 1 × 107 stem cells per dose (subcutaneously administered in eight areas surrounding wound margin) on day 7; and group IV, rats receiving stem cells on days 7 and 10. Wound healing was assessed clinically. Histologic examination was performed with hematoxylin and eosin staining. CD45, Ki-67, prolyl 4-hydroxylase, epidermal growth factor, and vascular endothelial growth factor were evaluated with immunohistochemical analysis.

Results: Overall clinical results showed that wound size was significantly reduced in mesenchymal stem cell–treated rats as compared with controls. Complete wound-healing time was statistically shorter in rats treated once as compared with controls (6.6 ± 1.13 weeks versus 9.8 ± 0.75 weeks; p < 0.001). It was significantly shorter in rats treated with mesenchymal stem cells twice as compared with rats treated once (5.2 ± 0.75 weeks versus 6.6 ± 1.13 weeks; p = 0.026). Histologic analysis revealed significant reduction in topical proinflammatory reaction and suppression of CD45 expression in the mesenchymal stem cell group as compared with the control group. On immunohistochemistry analysis, significant increases in epidermal growth factor, vascular endothelial growth factor, prolyl 4-hydroxylase, and Ki-67 expression were noted in the treated group as compared with the control group.

Conclusions: Mesenchymal stem cells significantly enhanced diabetic wound healing. Treatment with them is associated with increases of biomarkers in tissue regeneration.

Kaohsiung, Taiwan

From the Departments of Plastic and Reconstructive Surgery, Medical Research, and Orthopedics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, and the Department of Biological Sciences, National Sun Yat-sen University.

Received for publication July 28, 2010; revised January 10, 2011.

Presented at the 10th Congress of the International Confederation for Plastic Reconstructive and Aesthetic Surgery, in Tokyo, Japan, October 9 through 10, 2009.

Disclosure: The authors have no financial interest to declare in relation to the content of this article.

Yur-Ren Kuo, M.D., Ph.D.; Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung 83305, Taiwan, t1207816@ms22.hinet.net kuoyr@adm.cgmh.org.tw

©2011American Society of Plastic Surgeons