Exosomes derived from umbilical cord-mesenchymal stem cells inhibit the NF-κB/MAPK signaling pathway and reduce the inflammatory response to promote recovery from spinal cord injury.

ABSTRACT

Spinal cord injury (SCI) is a serious traumatic disease of the central nervous system and leads to incomplete or complete loss of the body's autonomous motor and sensory functions, seriously endangering human health. Recently, exosomes have been proposed as important substances in cell-to-cell interactions. Mesenchymal stem cell (MSC)-derived exosomes exert good therapeutic effects and play a crucial role in neurological damage repair. However, the detailed mechanisms underlying their effects remain unknown. Herein, we found that compared to SCI rats, those subjected to umbilical cord MSC (UC-MSC)-derived exosomes injection showed an improved motor ability. Nevertheless, the transcriptome of BV2 microglia in different treatment groups indicated that the action pathway of exosomes might be the NF-κB/MAPK pathway. Additionally, exosomes from UC-MSCs could inhibit P38, JNK, ERK, and P65 phosphorylation in BV2 microglia and SCI rat tissues. Moreover, exosomes could inhibit apoptosis and inflammatory reaction and reactive oxygen species (ROS) production of BV2 microglia in vitro and in vivo. In conclusion, UC-MSCs-derived exosomes might protect SCI in rats by inhibiting inflammatory response via the NF-κB/MAPK signaling pathway, representing novel treatment targets or approaches for SCI.