Bone marrow mesenchymal stem cell-derived exosomes promote the recovery of spinal cord injury and inhibit ferroptosis by inactivating IL-17 pathway

Mesenchymal stem cell (MSC)-derived exosomes are considered as an alternative to cell therapy in various diseases. This study aimed to understand the effect of bone marrow MSC-derived exosomes (BMMSC-exos) on spinal cord injury (SCI) and unveil its regulatory mechanism on ferroptosis. Exosomes were isolated from BMMSCs and the uptake of BMMSCs-exos by PC12 cells were determined using PKH67 staining. The effect of BMMSC-exos on SCI in rats was studied by evaluating pathological changes of spinal cord tissues, inflammatory cytokines and ferroptosis-related proteins. Transcriptome sequencing was used to discover the differential expressed genes (DEGs) between SCI rats and BMMSC-exos-treated rats followed by functional enrichment analyses. The effect of BMMSC-exos on ferroptosis and interleukin 17 (IL-17) pathway was evaluated in oxygen-glucose deprivation (OGD)-treated PC12 cells. The particles extracted from BMMSC cells were exosomes that could be taken up by PC12 cells. BMMSC-exos treatment ameliorates injuries of spinal cord, suppressed the accumulation of Fe2+, malondialdehyde (MDA) and reactive oxygen species (ROS) and elevated the level of glutathione (GSH). Also, BMMSC-exos downregulated the expression of acyl-CoA synthetase long chain family member 4 (ACSL4) and upregulated glutathione peroxidase 4 (GPX4) and cysteine/glutamate antiporter xCT. A total of 110 DEGs were discovered and they were mainly enriched in IL-17 signaling pathway. Further in vitro experiments showed that BMMSC-exos alleviated OGD-induced ferroptosis and inactivated IL-17 pathway.