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嗅黏膜间质基质细胞移植通过诱导小胶质细胞极化修复脊髓损伤。

Transplantation of olfactory mucosa mesenchymal stromal cells repairs spinal cord injury by inducing microglial polarization.

机构信息

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.

出版信息

Spinal Cord. 2024 Aug;62(8):429-439. doi: 10.1038/s41393-024-01004-6. Epub 2024 Jun 7.

Abstract

STUDY DESIGN

Animal studies OBJECTIVES: To evaluate the therapeutic effect of olfactory mucosa mesenchymal stem cell (OM-MSCs) transplantation in mice with spinal cord injury (SCI) and to explore the mechanism by which OM-MSCs inhibit neuroinflammation and improve SCI.

SETTING

Xiangya Hospital, Central South University; Affiliated Hospital of Guangdong Medical University.

METHODS

Mice (C57BL/6, female, 6-week-old) were randomly divided into sham, SCI, and SCI + OM-MSC groups. The SCI mouse model was generated using Allen's method. OM-MSCs were immediately delivered to the lateral ventricle after SCI using stereotaxic brain injections. One day prior to injury and on days 1, 5, 7, 14, 21, and 28 post-injury, the Basso Mouse Scale and Rivlin inclined plate tests were performed. Inflammation and microglial polarization were evaluated using histological staining, immunofluorescence, and qRT-PCR.

RESULTS

OM-MSCs originating from the neuroectoderm have great potential in the management of SCI owing to their immunomodulatory effects. OM-MSCs administration improved motor function, alleviated inflammation, promoted the transformation of the M1 phenotype of microglia into the M2 phenotype, facilitated axonal regeneration, and relieved spinal cord injury in SCI mice.

CONCLUSIONS

OM-MSCs reduced the level of inflammation in the spinal cord tissue, protected neurons, and repaired spinal cord injury by regulating the M1/M2 polarization of microglia.

摘要

研究设计

动物研究

目的

评估嗅黏膜间充质干细胞(OM-MSCs)移植治疗脊髓损伤(SCI)小鼠的疗效,并探讨 OM-MSCs 抑制神经炎症和改善 SCI 的机制。

设置

中南大学湘雅医院;广东医科大学附属医院。

方法

将 6 周龄雌性 C57BL/6 小鼠随机分为假手术组、SCI 组和 SCI+OM-MSC 组。采用 Allen 法建立 SCI 小鼠模型。SCI 后立即通过立体定向脑注射将 OM-MSCs 递送至侧脑室。在损伤前 1 天和损伤后 1、5、7、14、21 和 28 天,进行 Basso 小鼠量表和 Rivlin 斜面板测试。采用组织学染色、免疫荧光和 qRT-PCR 评估炎症和小胶质细胞极化。

结果

来源于神经外胚层的 OM-MSCs 具有免疫调节作用,在 SCI 治疗中有很大的潜力。OM-MSCs 给药改善了运动功能,减轻了炎症,促进了小胶质细胞 M1 表型向 M2 表型的转化,促进了轴突再生,并缓解了 SCI 小鼠的脊髓损伤。

结论

OM-MSCs 通过调节小胶质细胞 M1/M2 极化,降低脊髓组织炎症水平,保护神经元,修复脊髓损伤。

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