Mesenchymal stem cells deliver exogenous miR-21 via exosomes to inhibit nucleus pulposus cell apoptosis and reduce intervertebral disc degeneration.

Although mesenchymal stem cells ( MSCs) transplantation into the IVD (intervertebral disc) may be beneficial in inhibiting apoptosis of nucleus pulposus cells ( NPCs) and alleviating IVD degeneration, the underlying mechanism of this therapeutic process has not been fully explained. The purpose of this study was to explore the protective effect of MSC-derived exosomes ( MSC-exosomes) on NPC apoptosis and IVD degeneration and investigate the regulatory effect of mi RNAs in MSC-exosomes and associated mechanisms for NPC apoptosis. MSC-exosomes were isolated from MSC medium, and its anti-apoptotic effect was assessed in a cell and rat model. The down-regulated mi RNAs in apoptotic NPCs were identified, and their contents in MSC-exosomes were detected. The target genes of eligible mi RNAs and possible downstream pathway were investigated. Purified MSC-exosomes were taken up by NPCs and suppressed NPC apoptosis. The levels of miR-21 were down-regulated in apoptotic NPCs while MSC-exosomes were enriched in miR-21. The exosomal miR-21 could be transferred into NPCs and alleviated TNF-α induced NPC apoptosis by targeting phosphatase and tensin homolog ( PTEN) through phosphatidylinositol 3-kinase ( PI3K)-Akt pathway. Intradiscal injection of MSC-exosomes alleviated the NPC apoptosis and IVD degeneration in the rat model. In conclusion, MSC-derived exosomes prevent NPCs from apoptotic process and alleviate IVD degeneration, at least partly, via miR-21 contained in exosomes. Exosomal miR-21 restrains PTEN and thus activates PI3K/Akt pathway in apoptotic NPCs. Our work confers a promising therapeutic strategy for IVD degeneration. [ABSTRACT FROM AUTHOR]