Nasal mucosal mesenchymal stem cells promote repair of sciatic nerve injury in rats by modulating the inflammatory microenvironment

Abstract

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.