Zhou Dan, Zhai Wei, Zhang Miaomiao
School of Medicine, Jiangsu University Zhenjiang, Jiangsu, P. R. China.
Department of Laboratory Medicine, Jintan Hospital, Jiangsu University Jintan, Jiangsu, P. R. China.
Int J Clin Exp Pathol. 2018 Nov 1;11(11):5157-5170. eCollection 2018.
Mesenchymal stem cells (MSCs) are known for their capacity to produce extracellular vesicles (EVs), which are key mediators of information transfer between different cells for tissue repair and regeneration. Schwann cells are the major glial cells of the peripheral nervous system and play a key role in the survival, function, and regeneration of neurons. However, the action of MSC-derived EVs (MSC-EVs) on Schwann cells remains unclear. In the present study, we investigated the effect of rat bone marrow MSC-EVs on RSC96 Schwann cells. EVs derived from Rat bone marrow MSCs were isolated by ultracentrifugation and characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The effects of MSC-EVs on RSC96 cell proliferation, migration, apoptosis, and the protein levels were analyzed using the MTT and Colony-forming assays, the Transwell and wound healing assays, flow cytometry, and western blot, respectively. We found that rat MSCs secreted 80-400 nm heterogeneous small vesicles, which were defined as EVs. Incubation of RSC96 cells with rat MSC-EVs resulted in the uptake of EVs by the cells. MSC-EV treatment significantly inhibited RSC96 cell proliferation and migration, promoted their apoptosis, and activated the ERK pathway, while ERK signal repression using U0126 exhibited the opposite effects. Our data showed that MSC-EVs inhibited proliferation and migration and promoted apoptosis through the activation of the ERK pathway in RSC96 cells. Thus, the effect of BMSC-EVs on RSC96 cells may affect peripheral nerve injury and repair, as mediated by Schwann cells.
间充质干细胞（MSCs）以其产生细胞外囊泡（EVs）的能力而闻名，这些囊泡是不同细胞之间进行组织修复和再生信息传递的关键介质。雪旺细胞是周围神经系统的主要神经胶质细胞，在神经元的存活、功能和再生中起关键作用。然而，间充质干细胞来源的细胞外囊泡（MSC-EVs）对雪旺细胞的作用仍不清楚。在本研究中，我们研究了大鼠骨髓MSC-EVs对RSC96雪旺细胞的影响。通过超速离心分离大鼠骨髓间充质干细胞来源的细胞外囊泡，并通过透射电子显微镜（TEM）和扫描电子显微镜（SEM）进行表征。分别使用MTT和集落形成试验、Transwell和伤口愈合试验、流式细胞术和蛋白质印迹分析了MSC-EVs对RSC96细胞增殖、迁移、凋亡和蛋白质水平的影响。我们发现大鼠间充质干细胞分泌80-400nm的异质小囊泡，这些囊泡被定义为细胞外囊泡。用大鼠MSC-EVs孵育RSC96细胞导致细胞摄取细胞外囊泡。MSC-EV处理显著抑制RSC96细胞增殖和迁移，促进其凋亡，并激活ERK途径，而使用U0126抑制ERK信号则表现出相反的效果。我们的数据表明，MSC-EVs通过激活RSC96细胞中的ERK途径抑制增殖和迁移并促进凋亡。因此，骨髓间充质干细胞来源的细胞外囊泡对RSC96细胞的作用可能会影响由雪旺细胞介导的周围神经损伤和修复。
