Gingiva-Derived Mesenchymal Stem Cell-Extracellular Vesicles Activate Schwann Cell Repair Phenotype and Promote Nerve Regeneration

牙龈间充质干细胞-细胞外囊泡激活雪旺细胞修复表型并促进神经再生

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作者:Qin Mao, Phuong D Nguyen, Rabie M Shanti, Shihong Shi, Pasha Shakoori, Qunzhou Zhang, Anh D Le

Abstract

Peripheral nerve injuries (PNIs) are common and debilitating, usually resulting in considerable long-term disability and remaining an unmet clinical need. Even though the combination of mesenchymal stem cells (MSCs) and the state-of-the-art tissue engineering technologies has shown promising therapeutic potentials for PNI, there is still not a single licensed stem cell-based product for peripheral nerve repair/regeneration. Emerging evidence indicates that MSC-derived extracellular vesicles (EVs) are comparably effective as MSCs in the therapy of a variety of disease models or pathological conditions. This report shows that local delivery of gingiva-derived mesenchymal stem cell (GMSC)-derived EVs could obviously promote axonal regeneration and functional recovery of injured mice sciatic nerves. Importantly, the findings suggest that GMSC-derived EVs promoted the expression of Schwann cell dedifferentiation/repair phenotype-related genes in vitro, particularly c-JUN, a key transcription factor that drives the activation of repair phenotype of Schwann cells during PNI and regeneration.

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