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Human Neural Stem Cell-Conditioned Medium Inhibits Inflammation in Macrophages Via Sirt-1 Signaling Pathway In Vitro and Promotes Sciatic Nerve Injury Recovery in Rats.
Stem Cells and Development ( IF 2.5 ) Pub Date : 2020-08-14 , DOI: 10.1089/scd.2020.0020
Tianyan Chen 1 , Yilei Li 1 , Wei Ni 1 , Bin Tang 1 , Yusheng Wei 1 , Jing Li 1 , Jiahong Yu 1 , Lei Zhang 1 , Jianyi Gao 1 , Jiqin Zhou 1 , Weining Zhang 1 , Hong Xu 2 , Jiabo Hu 1
Affiliation  

Chronic persistent inflammation is thought to impede axon regeneration and cause demyelinating disease also with neuropathic pain, leading to more severe dysfunction after peripheral nerve injury. Increasing evidence indicates that neural stem cells (NSCs) have immunomodulatory effects, and previous studies have shown that many of the beneficial effects attributed to stem cell therapy may exert their therapeutic effects through paracrine mechanisms. In this research, the repairing effect of NSC-conditioned medium (NSC-CM) on sciatic nerve injury and its mechanism of repair were further explored. The present research showed that NSC-CM promoted histopathological and functional recovery after crush injury in rats, and what counts is that NSC-CM inhibited the inflammation of sciatic nerve in the late stage of injury. NSC-CM significantly downregulated the infiltration of proinflammatory factors [tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and IL-1β] as well as decreased the CD68 inflammatory macrophages infiltrating in the sciatic nerve. In addition, to study the effect of NSC-CM on the inflammatory state of macrophages in vitro, lipopolysaccharide (LPS) was used to induce the proinflammation of macrophages. The results showed that NSC-CM decreased the expression of macrophage proinflammatory-related proteins (IL-6, IL-1β, TNF-α, inducible nitric oxide synthase) induced by LPS. The activation of Sirt-1 signaling in macrophages effectively countered the proinflammation induced by LPS in the presence of NSC-CM. Using Sirt-1-specific inhibitor EX527 partially weakened the anti-inflammatory effect of NSC-CM. Altogether, this study demonstrated for the first time that NSC-CM promotes functional recovery after sciatic nerve crush injury in vivo and also inhibits the inflammation in activated macrophages by activating Sirt-1 signaling pathway in vitro.

中文翻译:

人神经干细胞条件培养基在体外通过 Sirt-1 信号通路抑制巨噬细胞的炎症,并促进大鼠坐骨神经损伤的恢复。

慢性持续性炎症被认为会阻碍轴突再生并导致脱髓鞘疾病以及神经性疼痛,导致周围神经损伤后更严重的功能障碍。越来越多的证据表明神经干细胞 (NSCs) 具有免疫调节作用,之前的研究表明,归因于干细胞治疗的许多有益作用可能通过旁分泌机制发挥其治疗作用。本研究进一步探讨了NSC条件培养基(NSC-CM)对坐骨神经损伤的修复作用及其修复机制。目前的研究表明,NSC-CM促进了大鼠挤压伤后组织病理学和功能的恢复,重要的是NSC-CM在损伤后期抑制了坐骨神经的炎症。NSC-CM 显着下调促炎因子 [肿瘤坏死因子 α (TNF-α)、白介素 6 (IL-6) 和 IL-1β] 的浸润,并减少 CD68 炎性巨噬细胞浸润坐骨神经。此外,为了研究 NSC-CM 在体外对巨噬细胞炎症状态的影响,使用脂多糖 (LPS) 诱导巨噬细胞的炎症。结果表明,NSC-CM 降低了 LPS 诱导的巨噬细胞促炎相关蛋白(IL-6、IL-1β、TNF-α、诱导型一氧化氮合酶)的表达。在 NSC-CM 存在下,巨噬细胞中 Sirt-1 信号传导的激活有效地对抗了 LPS 诱导的促炎症。使用 Sirt-1 特异性抑制剂 EX527 部分削弱了 NSC-CM 的抗炎作用。共,
更新日期:2020-08-19
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