title: Bone marrow-derived mesenchymal stem cells enhanced diabetic wound healing through recruitment of tissue regeneration in a rat model of streptozotocin-induced diabetes.
abstract: 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.
authors.affiliation: 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.
authors.forename: Yur-Ren
authors.initials: YR
authors.lastname: Kuo
authors.forename: Chun-Ting
authors.initials: CT
authors.lastname: Wang
authors.forename: Jiin-Tsuey
authors.initials: JT
authors.lastname: Cheng
authors.forename: Feng-Sheng
authors.initials: FS
authors.lastname: Wang
authors.forename: Yuan-Cheng
authors.initials: YC
authors.lastname: Chiang
authors.forename: Ching-Jen
authors.initials: CJ
authors.lastname: Wang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001853:Bone Marrow; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D004817:Epidermis / Q000502:physiology*; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012038:Regeneration / Q000502:physiology; D012867:Skin / Q000293:injuries; D016896:Treatment Outcome; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000150:complications / Q000628:therapy*