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

Although mesenchymal stem cells ( MSC s) transplantation into the IVD (intervertebral disc) may be beneficial in inhibiting apoptosis of nucleus pulposus cells ( NPC s) 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 RNA s 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 RNA s in apoptotic NPC s were identified, and their contents in MSC ‐exosomes were detected. The target genes of eligible mi RNA s and possible downstream pathway were investigated. Purified MSC ‐exosomes were taken up by NPC s and suppressed NPC apoptosis. The levels of miR‐21 were down‐regulated in apoptotic NPC s while MSC ‐exosomes were enriched in miR‐21. The exosomal miR‐21 could be transferred into NPC s and alleviated TNF ‐α induced NPC apoptosis by targeting phosphatase and tensin homolog ( PTEN ) through phosphatidylinositol 3‐kinase ( PI 3K)‐Akt pathway. Intradiscal injection of MSC ‐exosomes alleviated the NPC apoptosis and IVD degeneration in the rat model. In conclusion, MSC ‐derived exosomes prevent NPC s from apoptotic process and alleviate IVD degeneration, at least partly, via miR‐21 contained in exosomes. Exosomal miR‐21 restrains PTEN and thus activates PI 3K/Akt pathway in apoptotic NPC s. Our work confers a promising therapeutic strategy for IVD degeneration.