Mesenchymal stem cells-derived exosomes ameliorate intervertebral disc degeneration through inhibiting pyroptosis

Abstract

Mesenchymal stem cell (MSCs)-based therapies have shown a promised result for intervertebral disc degeneration (IVDD) treatment. However, its molecular mechanisms remain unclear. Exosomes involve cell-cell communication via transference of its contents among different cells, and the present potential effect on cell death regulation. This study aimed to investigate the role of MSCs-derived exosomes on IVDD formation. Here, we first found the NLRP3-mediated nucleus pulposus cell (NP cell) pyroptosis was activated in the IVDD mice model and lipopolysaccharide (LPS)-induced model. However, MSCs treatment could inhibit NP cell pyroptosis in vitro. We then isolated MSCs-derived exosomes by differential centrifugation and identified the characteristics. Secondly, we investigated the function of MSCs-derived exosomes on LPS-induced NP cell pyroptosis. Finally, we presented evidence that MSCs-derived exosomal miR-410 was a crucial regulator of pyroptosis. Results showed that MSCs-derived exosomes play an anti-pyroptosis role by suppressing the NLRP3 pathway. Moreover, it suggested that this effect was attributed to miR-410, which was derived from MSCs-exosomes and could directly bind to NLRP3mRNA. In conclusion, for the first time, we demonstrated that MSCs-exosome treatment may inhibit pyroptosis and could be a promising therapeutic strategy for IVDD.

Keywords: IVDD; MSCs; exosomes; miR-410; pyroptosis.