Mesenchymal Stem Cell-Derived Exosomes Promote Recovery of The Facial Nerve Injury through Regulating Macrophage M1 and M2 Polarization by Targeting the P38 MAPK/NF-Κb Pathway

Abstract

Facial nerve (FN) injury seriously affects human social viability and causes a heavy economic and social burden. Although mesenchymal stem cell-derived exosomes (MSC-Exos) promise therapeutic benefits for injury repair, there has been no evaluation of the impact of MSC-Exos administration on FN repair. Herein, we explore the function of MSC-Exos in the immunomodulation of macrophages and their effects in repairing FN injury. An ultracentrifugation technique was used to separate exosomes from the MSC supernatant. Administrating MSC-Exos to SD rats via local injection after FN injury promoted axon regeneration and myelination and alleviated local and systemic inflammation. MSC-Exos facilitated M2 polarization and reduced the M1-M2 polarization ratio. miRNA sequencing of MSC-Exos and previous literature showed that the MAPK/NF-κb pathway was a downstream target of macrophage polarization. We confirmed this hypothesis both in vivo and in vitro. Our findings show that MSC-Exos are a potential candidate for treating FN injury because they may have superior benefits for FN injury recovery and can decrease inflammation by controlling the heterogeneity of macrophages, which is regulated by the p38 MAPK/NF-κb pathway.

Exploration of altered miRNA expression and function in MSC-derived extracellular vesicles in response to hydatid antigen stimulation

“…These pathways play important roles in cell functions such as adhesion, migration, survival, and differentiation ( Chen J. et al, 2020 ; Kodali et al, 2023 ; Lu et al, 2023 ; Xiong et al, 2023 ). Ras proteins, regulated by the MAPK pathway, are critical for bone formation and remodeling ( Sharma et al, 2013 ; Feng et al, 2016 ; Xue et al, 2023 ). MSCs EVs have been shown to enhance anti-inflammatory capacity, promote osteoblast function, and regulate macrophage polarization through the MAPK pathway ( Xue et al, 2023 ).…”

“…Ras proteins, regulated by the MAPK pathway, are critical for bone formation and remodeling ( Sharma et al, 2013 ; Feng et al, 2016 ; Xue et al, 2023 ). MSCs EVs have been shown to enhance anti-inflammatory capacity, promote osteoblast function, and regulate macrophage polarization through the MAPK pathway ( Xue et al, 2023 ). Additionally, the ESPs group showed enrichment in the Th17-related pathway, which is involved in inflammatory responses ( Kay et al, 2021 ).…”