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

IF 3.4 3区生物学 Q3 CELL BIOLOGY Human Cell 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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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.

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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。

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来源期刊

Human Cell CELL BIOLOGY-

CiteScore

5.90

自引率

2.30%

发文量

176

审稿时长

4.5 months

期刊介绍： Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well. Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format. Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.