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Mesenchymal stem cells deliver exogenous miR-21 via exosomes to inhibit nucleus pulposus cell apoptosis and reduce intervertebral disc degeneration.
- Source :
-
Journal of cellular and molecular medicine [J Cell Mol Med] 2018 Jan; Vol. 22 (1), pp. 261-276. Date of Electronic Publication: 2017 Aug 14. - Publication Year :
- 2018
-
Abstract
- 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 miRNAs 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 miRNAs in apoptotic NPCs were identified, and their contents in MSC-exosomes were detected. The target genes of eligible miRNAs 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.<br /> (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)
- Subjects :
- Adult
Animals
Culture Media, Conditioned pharmacology
Exosomes ultrastructure
Female
Humans
Male
Mesenchymal Stem Cells drug effects
MicroRNAs genetics
Middle Aged
Nucleus Pulposus drug effects
Rats, Sprague-Dawley
Tumor Necrosis Factor-alpha pharmacology
Young Adult
Apoptosis drug effects
Exosomes metabolism
Intervertebral Disc Degeneration pathology
Mesenchymal Stem Cells metabolism
MicroRNAs administration & dosage
Nucleus Pulposus metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1582-4934
- Volume :
- 22
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of cellular and molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 28805297
- Full Text :
- https://doi.org/10.1111/jcmm.13316