Mesenchymal Stem Cell Derived Exosomes Suppress Neuronal Cell Ferroptosis Via lncGm36569/miR-5627-5p/FSP1 Axis in Acute Spinal Cord Injury

Exosomes derived from mesenchymal stem cells (MSCs) have been considered as an alternative for cell therapy of acute spinal cord injury (ASCI). However, the underlying mechanism remains unclear. Here, ASCI mouse model and hypoxic cell model were established to evaluate the effects of MSCs and MSCs-derived exosomes (MSCs-exo). The results showed that both MSCs and MSCs-exo inhibited the production of ROS and ferrous iron, upregulated the expression of ferroptosis suppressor FSP1, and enhanced repair of neurological function in the ASCI mice. Besides, MSCs and MSCs-exo attenuated hypoxia-induced neuronal cell ferroptosis and increased cell proliferation. Further study demonstrated that lncGm36569 was enriched in the MSCs-exo. Through bioinformatics analysis and luciferase assay, we confirmed that lncGm36569 acted as a competitive RNA of miR-5627-5p to induce FSP1 upregulation. Furthermore, overexpression of miR-5627-5p reversed the therapeutic effects of lncGm36569 on neuronal cell ferroptosis. In conclusion, MSCs-exosomes lncGm36569 inhibited neuronal cell ferroptosis through miR-5627-5p/FSP1 axis, thereby attenuating neuronal dysfunction. Graphical Abstract