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白细胞介素-10过表达的骨髓间充质干细胞移植改善糖尿病诱导的小鼠骨折愈合受损情况。

Transplantation of IL-10-Overexpressing Bone Marrow-Derived Mesenchymal Stem Cells Ameliorates Diabetic-Induced Impaired Fracture Healing in Mice.

作者信息

Cui Keze, Chen Yuanliang, Zhong Haibo, Wang Nan, Zhou Lihui, Jiang Fusong

机构信息

Haikou Orthopedic and Diabetes Hospital of Shanghai Sixth People's Hospital, Hainan, 570311 China.

Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 Henan China.

出版信息

Cell Mol Bioeng. 2019 Dec 23;13(2):155-163. doi: 10.1007/s12195-019-00608-w. eCollection 2020 Apr.

Abstract

BACKGROUND

Diabetes mellitus is characterized by hyperglycemia which displays insufficiency or resistance to insulin. One of the complications of diabetes is the increased risk of fracture and the impairment of bone repair and regulation. There have been evidences from previous studies that mesenchymal stem cells (MSCs) from bone marrow promote cartilage and callous formation. In addition, IL-10, an anti-inflammatory cytokine, has been observed to relieve inflammation-related complications in diabetes.

METHODS

In this study, the role of IL-10-overexpressing bone marrow-derived MSCs (BM-MSCs) was examined in the diabetic mice model with femur fracture. MSCs were isolated from the BALB/c mice and IL-10 over expression was conducted with lentivirus transduction. The streptozotocin (STZ)-induced diabetes model with femoral fracture was established. BM-MSCs with IL-10 over expression were transplanted into the fracture area. The expressions of inflammatory factors IL-6, TNF-α and INF-γ were examined by qPCR and immunoblot; the biomechanical strength of the fracture site of the mice was examined and evaluated.

RESULTS

Data showed that IL-10 overexpressed BM-MSCs transplantation decreased inflammatory response, promoted bone formation, and increased the strength of the fracture site in STZ-induced diabetic mice with femoral fracture.

CONCLUSION

IL-10 overexpressed BM-MSCs transplantation accelerated fracture repair in STZ-induced diabetic mice, which in turn provides potential clinical application prospects.

摘要

背景

糖尿病的特征是高血糖,表现为胰岛素分泌不足或抵抗。糖尿病的并发症之一是骨折风险增加以及骨修复和调节受损。先前的研究已有证据表明,骨髓间充质干细胞(MSCs)可促进软骨和骨痂形成。此外,已观察到抗炎细胞因子白细胞介素-10(IL-10)可缓解糖尿病中与炎症相关的并发症。

方法

在本研究中,检测了过表达IL-10的骨髓来源间充质干细胞(BM-MSCs)在股骨骨折糖尿病小鼠模型中的作用。从BALB/c小鼠中分离出MSCs,并通过慢病毒转导进行IL-10过表达。建立链脲佐菌素(STZ)诱导的股骨骨折糖尿病模型。将过表达IL-10的BM-MSCs移植到骨折部位。通过qPCR和免疫印迹检测炎症因子IL-6、肿瘤坏死因子-α(TNF-α)和干扰素-γ(INF-γ)水平;检测并评估小鼠骨折部位的生物力学强度。

结果

数据显示,过表达IL-10的BM-MSCs移植可减轻STZ诱导的股骨骨折糖尿病小鼠的炎症反应,促进骨形成,并增加骨折部位的强度。

结论

过表达IL-10的BM-MSCs移植可加速STZ诱导的糖尿病小鼠的骨折修复,这反过来提供了潜在的临床应用前景。

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