Bone marrow mesenchymal stem cells-derived exosomes promote spinal cord injury repair through the miR-497-5p/TXNIP/NLRP3 axis

Abstract

Bone marrow mesenchymal stem cells (BMSCs) indicate a repairing prospect to treat spinal cord injury, a major traumatic disease. This study investigated the repair effect of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) on spinal cord injury. BMSCs were collected to extract BMSC-Exos which were identified by different means. The SCI model of rats was established, the motor behavior was scored by BBB field test, and the spinal cord tissues were separated and stained by HE, Nissl, and Tunel, respectively, as well as analyzed to measure inflammatory and oxidative stress responses. PC12 cells were co-cultured with Exos and analyzed by CCK-8 and flow cytometry to measure cell proliferation and apoptosis. BMSC-Exos improved SCI in rats with the recovery of motor function, alleviation of pathological conditions, and reduction of apoptosis, inflammatory responses, and oxidative stress. BMSC-Exos increased miR-497-5p expression, and miR-497-5p overexpression strengthened the protective effect of BMSC-Exos on SCI. miR-497-5p targeted inactivation of TXNIP/NLRP3 pathway. TXNIP saved the repair effect of miR-497-5p-carrying BMSC-Exos on SCI rats. miR-497-5p-carrying BMSC-Exos alleviated apoptosis and induced proliferation of H₂O₂-treated PC12 cells. BMSC-Exos promote SCI repair via the miR-497-5p/TXNIP/NLRP3 axis, which may be a target for alleviating SCI-associated nerve damage.