Bone marrow mesenchymal stem cells-derived exosomes repair degenerative intervertebral discs by modulating macrophage M1/M2 phenotype.

Abstract

The effect of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) on intervertebral disc degeneration (IVDD) repair and healing and its possible mechanism were investigated. Tail IVDD puncture was performed on mice, and BMSC-Exos were injected into the joint cavity. The disc morphology was observed by HE staining, apoptosis rate of nucleus pulposus (NP) tissues was determined by TUNEL, and polarization of macrophages and NP cell damage were detected by Western Blot. An in vitro experimental model was established by co-culture of nucleus pulposus (NP) cells and M1 macrophages in a conditioned medium, and the improvement effect of BMSC-Exos on the proliferation of damaged NP cells was detected by CCK-8 assay. NP cell apoptosis was determined by flow cytometry. Inflammatory factors in NP cell supernatant was measured by ELISA. In results: BMSC-Exos reversed the degenerative changes of IVDD in mice. BMSC-Exos promoted the transformation of THP-1 cells from M1 to M2 and inhibited the release of inflammatory cytokines. BMSC-Exos inhibited matrix metallopeptidase 13 (MMP-13), matrix metallopeptidase 3 (MMP-3), and Cleaved caspase-3 expression in damaged NP tissues. BMSC-Exos significantly increased NP cell proliferation and blocked apoptosis. The concentration of inflammatory factors in the supernatant of NP cells treated with BMSC-Exos was significantly down-regulated. Conclusion: BMSC-Exos have a regenerative effect on IVDD, encourage macrophages to transform from M1 to M2, suppress NP cell apoptosis and inflammatory responses, and improve degenerative alterations in the intervertebral disc.