Adipose-derived mesenchymal stem cell exosomes ameliorate spinal cord injury in rats by activating the Nrf2/HO-1 pathway and regulating microglial polarization.

IF 1.5 4区 医学 Q4 NEUROSCIENCES Folia neuropathologica Pub Date : 2023-01-01 DOI:10.5114/fn.2023.130455
Yi Luo, You-Zhi He, Yong-Fu Wang, Yu-Xia Xu, Li Yang
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Abstract

As of now, there are no satisfactory treatments for spinal cord injury (SCI), so new therapeutic approaches are necessary to be explored. Adipose-derived mesenchymal stem cell exosomes (ADMSC-Exo), delightfully, show remarkable therapeutic effects. Therefore, we try to investigate the effects and mechanisms of ADMSC-Exo on SCI, as well as to provide novel approaches for the treatment of SCI. Adipose-derived mesenchymal stem cells (ADMSC) were isolated from rats and then exosomes (Exo) were extracted from the cells. The extracted Exo were identified by flow cytometry, transmission electron microscopy and nanoparticle tracking analysis (NTA). Then, the SCI rat model was established by the spinal cord impactor and injected with 200 µl PBS or Exo into their tail veins at 30 min, 24 h, and 48 h after surgery. The rats in the Control group and Exo group only exposed the spine. Motor function recovery was assessed on days 0, 7, 14, 21, and 28; histopathological changes and apoptosis levels in spinal cord tissues were observed by HE staining and TUNEL staining; the levels of inflammatory cytokines TNF-a, IL-6, and MCP-1 in spinal cord tissues were measured by ELISA; the expression levels of iNOS, IL-12, Arg1, and Mrc1 in spinal cord tissues were detected by qRT-PCR; and Nrf2, HO-1, and NQO1 protein expression in spinal cord tissues were detected by Western blot. ADMSC-Exo were successfully isolated and identified. ADMSC-Exo significantly relieved SCI and promoted motor function recovery in SCI rats. Moreover, ADMSC-Exo inhibited the expression of both inflammatory factors in the spinal cord tissues and M1 microglia, promoted the expression of M2 microglia, and activated the Nrf2/HO-1 pathway. Altogether, ADMSC-Exo can not only ameliorate SCI, but also promote the motor function recovery of rats. And the mechanism of ADMSC-Exo improving SCI may be achieved by activating Nrf2/HO-1 pathway and microglial polarization.

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脂肪来源的间充质干细胞外泌体通过激活Nrf2/HO-1通路和调节小胶质细胞极化来改善大鼠脊髓损伤。
到目前为止,脊髓损伤还没有令人满意的治疗方法,因此有必要探索新的治疗方法。脂肪来源的间充质干细胞外泌体(ADMSC-Exo)令人高兴地显示出显著的治疗效果。因此,我们试图研究ADMSC-Exo对SCI的作用和机制,并为SCI的治疗提供新的途径。从大鼠中分离脂肪来源的间充质干细胞(ADMSC),然后从细胞中提取外泌体(Exo)。通过流式细胞术、透射电子显微镜和纳米颗粒跟踪分析(NTA)对提取的Exo进行鉴定。然后,通过脊髓冲击器建立SCI大鼠模型,并在手术后30分钟、24小时和48小时向其尾静脉注射200µl PBS或Exo。对照组和Exo组大鼠仅暴露于脊柱。在第0、7、14、21和28天评估运动功能恢复情况;HE染色和TUNEL染色观察脊髓组织病理学变化和细胞凋亡水平;采用ELISA法测定脊髓组织中炎性细胞因子TNF-a、IL-6和MCP-1的水平;qRT-PCR检测脊髓组织中iNOS、IL-12、Arg1和Mrc1的表达水平;Western印迹检测脊髓组织中Nrf2、HO-1和NQO1蛋白的表达。ADMSC-Exo成功分离鉴定。ADMSC-Exo能显著减轻SCI大鼠的脊髓损伤,促进运动功能的恢复。此外,ADMSC-Exo抑制脊髓组织和M1小胶质细胞中炎症因子的表达,促进M2小胶质细胞的表达,并激活Nrf2/HO-1通路。总之,ADMSC-Exo不仅可以改善SCI,而且可以促进大鼠运动功能的恢复。ADMSC-Exo改善SCI的机制可能通过激活Nrf2/HO-1通路和小胶质细胞极化来实现。
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来源期刊
Folia neuropathologica
Folia neuropathologica 医学-病理学
CiteScore
2.50
自引率
5.00%
发文量
38
审稿时长
>12 weeks
期刊介绍: Folia Neuropathologica is an official journal of the Mossakowski Medical Research Centre Polish Academy of Sciences and the Polish Association of Neuropathologists. The journal publishes original articles and reviews that deal with all aspects of clinical and experimental neuropathology and related fields of neuroscience research. The scope of journal includes surgical and experimental pathomorphology, ultrastructure, immunohistochemistry, biochemistry and molecular biology of the nervous tissue. Papers on surgical neuropathology and neuroimaging are also welcome. The reports in other fields relevant to the understanding of human neuropathology might be considered.
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