Mesenchymal stem cell-derived extracellular vesicles promote apoptosis in RSC96 Schwann cells through the activation of the ERK pathway

Int J Clin Exp Pathol. 2018 Nov 1;11(11):5157-5170. eCollection 2018.

Abstract

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.

Keywords: ERK pathway; Mesenchymal stem cell; RSC96 Schwann cells; apoptosis; extracellular vesicles.