Tang Yushi, Li Yilu, Yang Wenhui, Tao Zhenxing, Shi Wentao, Yu Mengyuan, Xu Bai, Lu Xiaojie
Neuroscience Center, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu Province 214122, PR China; Wuxi neurosurgical Institute, Wuxi, Jiangsu Province, 214122, PR China.
Neuroscience Center, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu Province 214122, PR China.
Neurosci Lett. 2025 Feb 6;848:138112. doi: 10.1016/j.neulet.2024.138112. Epub 2024 Dec 30.
Sciatic nerve injury (SNI) represents the most prevalent form of peripheral nerve damage, resulting in the rapid activation of macrophages into the M1 phenotype following injury. This activation induces an inflammatory microenvironment that negatively impacts nerve regeneration. Ectodermal mesenchymal stem cells (EMSCs), isolated from nasal mucosa, possess the capacity for multidirectional differentiation and exhibit immunomodulatory effects. Modulating macrophage polarization to create a favorable environment for nerve repair may represent a potential approach to facilitate nerve recovery. This investigation sought to explore the effects of EMSCs transplantation on macrophage polarization and nerve regeneration in SNI, as well as to identify the underlying mechanisms. An in vivo SNI model was established, and behavioral and histological analyses demonstrated that EMSCs transplantation facilitated nerve function recovery. Furthermore, immunofluorescence and Western blot assays revealed an increase in M2 macrophage presence and the secretion of anti-inflammatory cytokines following EMSCs transplantation, thereby promoting nerve regeneration. In vitro, EMSCs were found to enhance M2 macrophage polarization and the production of anti-inflammatory factors. Additionally, it was confirmed that EMSCs regulate macrophage polarization through the PI3K/AKT/NF-κB signaling pathway, thereby fostering an optimal inflammatory environment for nerve regeneration.
坐骨神经损伤（SNI）是周围神经损伤最常见的形式，损伤后会迅速激活巨噬细胞转变为M1表型。这种激活会诱导炎症微环境，对神经再生产生负面影响。从鼻黏膜分离出的外胚层间充质干细胞（EMSCs）具有多向分化能力，并表现出免疫调节作用。调节巨噬细胞极化以创造有利于神经修复的环境可能是促进神经恢复的一种潜在方法。本研究旨在探讨EMSCs移植对SNI中巨噬细胞极化和神经再生的影响，并确定其潜在机制。建立了体内SNI模型，行为学和组织学分析表明EMSCs移植促进了神经功能恢复。此外，免疫荧光和蛋白质印迹分析显示，EMSCs移植后M2巨噬细胞数量增加，抗炎细胞因子分泌增多，从而促进了神经再生。在体外，发现EMSCs增强了M2巨噬细胞极化和抗炎因子的产生。此外，证实EMSCs通过PI3K/AKT/NF-κB信号通路调节巨噬细胞极化，从而为神经再生营造最佳的炎症环境。
