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骨髓间充质干细胞通过募集组织再生增强链脲佐菌素诱导糖尿病大鼠模型中的糖尿病创面愈合。

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

机构信息

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.

出版信息

Plast Reconstr Surg. 2011 Oct;128(4):872-880. doi: 10.1097/PRS.0b013e3182174329.

DOI:10.1097/PRS.0b013e3182174329
PMID:21921763
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.

摘要

背景

本研究旨在探讨骨髓间充质干细胞治疗是否通过组织再生增强糖尿病创面愈合的效果。

方法

作者使用链脲佐菌素诱导的糖尿病啮齿动物模型中的背侧皮肤缺损(6×5cm)。将 40 只雄性 Wistar 大鼠分为四组:I 组,非糖尿病大鼠(对照组);II 组,未接受间充质干细胞治疗的糖尿病对照组;III 组,在第 7 天接受 1×10 个细胞/剂量(皮下注射于伤口边缘周围的八个区域);IV 组,在第 7 天和第 10 天接受干细胞治疗。通过临床评估伤口愈合情况。苏木精和伊红染色进行组织学检查。免疫组织化学分析评估 CD45、Ki-67、脯氨酸 4-羟化酶、表皮生长因子和血管内皮生长因子。

结果

总体临床结果表明,与对照组相比,间充质干细胞治疗组的伤口面积显著缩小。与对照组相比,单次治疗的大鼠完全愈合时间明显缩短(6.6±1.13 周比 9.8±0.75 周;p<0.001)。与单次治疗相比,两次治疗的大鼠明显缩短(5.2±0.75 周比 6.6±1.13 周;p=0.026)。组织学分析显示,与对照组相比,间充质干细胞组局部促炎反应明显减轻,CD45 表达受到抑制。免疫组织化学分析显示,与对照组相比,治疗组表皮生长因子、血管内皮生长因子、脯氨酸 4-羟化酶和 Ki-67 的表达显著增加。

结论

间充质干细胞显著增强了糖尿病创面愈合。用它们治疗与组织再生生物标志物的增加有关。

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