Bone marrow-derived mesenchymal stem cells enhanced diabetic wound healing through recruitment of tissue regeneration in a rat model of streptozotocin-induced diabetes

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 × 10 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.