Delivery of neurotrophin-3 by RVG-Lamp2b-modified mesenchymal stem cell-derived exosomes alleviates facial nerve injury.

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
ACS Applied Electronic Materials Pub Date : 2024-09-01 Epub Date: 2024-06-11 DOI:10.1007/s13577-024-01086-7
Wenting Bi, Xiaodan Mu, Yongfeng Li, Qingyan Sun, Lei Xiang, Min Hu, Huawei Liu
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引用次数: 0

Abstract

We aim to investigate the effect of RVG-Lamp2b-modified exosomes (exos) loaded with neurotrophin-3 (NT-3) on facial nerve injury. Exos were collected from control cells (Ctrl Exo) or bone marrow mesenchymal stem cells co-transfected with RVG-Lamp2b and NT-3 plasmids (RVG-NT-3 Exo) by gradient centrifugation and identified by western blotting, transmission electron microscopy, and nanoparticle tracking analysis. Effect of RVG-NT-3 Exo on oxidative stress damage was determined by analysis of the morphology, viability, and ROS production of neurons. Effect of RVG-NT-3 Exo on facial nerve axotomy (FNA) was determined by detecting ROS production, neuroinflammatory reaction, microglia activation, facial motor neuron (FMN) death, and myelin sheath repair. Loading NT-3 and modifying with RVG-Lamp2b did not alter the properties of the exos. Moreover, RVG-NT-3 Exo could effectively target neurons to deliver NT-3. Treatment with RVG-NT-3 Exo lowered H2O2-induced oxidative stress damage in primary neurons and Nsc-34 cells. RVG-NT-3 Exo treatment significantly decreased ROS production, neuroinflammatory response, FMN death, and elevated microglia activation and myelin sheath repair in FNA rat models. Our findings suggested that RVG-NT-3 Exo-mediated delivery of NT-3 is effective for the treatment of facial nerve injury.

Abstract Image

通过RVG-Lamp2b修饰间充质干细胞衍生的外泌体输送神经营养素-3可减轻面神经损伤。
我们旨在研究含有神经营养素-3(NT-3)的RVG-Lamp2b修饰外泌体(exos)对面神经损伤的影响。通过梯度离心从对照细胞(Ctrl Exo)或共转染了RVG-Lamp2b和NT-3质粒的骨髓间充质干细胞(RVG-NT-3 Exo)中收集外泌体,并通过Western印迹、透射电子显微镜和纳米颗粒追踪分析进行鉴定。RVG-NT-3 Exo 对氧化应激损伤的影响是通过分析神经元的形态、存活率和 ROS 生成来确定的。通过检测 ROS 生成、神经炎症反应、小胶质细胞活化、面部运动神经元(FMN)死亡和髓鞘修复,确定了 RVG-NT-3 Exo 对面神经轴突切断术(FNA)的影响。加载 NT-3 并用 RVG-Lamp2b 修饰并不会改变外泌体的特性。此外,RVG-NT-3外泌体能有效靶向神经元输送NT-3。用RVG-NT-3 Exo处理原代神经元和Nsc-34细胞可降低H2O2诱导的氧化应激损伤。在 FNA 大鼠模型中,RVG-NT-3 Exo 治疗可显著减少 ROS 生成、神经炎症反应、FMN 死亡,并促进小胶质细胞活化和髓鞘修复。我们的研究结果表明,RVG-NT-3 Exo 介导的 NT-3 递送可有效治疗面神经损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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