Mesenchymal stem cell-derived exosomes ameliorate intervertebral disc degeneration via anti-oxidant and anti-inflammatory effects

Free Radic Biol Med. 2019 Nov 1;143:1-15. doi: 10.1016/j.freeradbiomed.2019.07.026. Epub 2019 Jul 24.

Abstract

Excessive oxidative stress and inflammation are the key early events in the development of intervertebral disc degeneration (IVDD). The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome has been identified as the major source of oxidative stress and the inflammatory responses and thus is an attractive therapeutic target for IVDD. However, currently, there are no reports on the use of mesenchymal stem cell (MSC)-derived exosomes to reduce NLRP3 inflammasome expression for IVDD treatment. The present study aimed to investigate the therapeutic effect of exosomes for use as IVDD therapeutics. We first manufactured and evaluated the characteristics of exosomes. Then, we investigated the effects of exosomes on H2O2-induced nucleus pulposus (NP) cell inflammation. Third, we tested the function of exosomes with respect to H2O2-induced ROS production and mitochondrial dysfunction. Finally, the therapeutic effect of exosomes on IVDD was investigated using a rabbit IVDD model. Results showed that exosomes play an anti-inflammatory role in pathological NP cells by suppressing inflammatory mediators and NLRP3 inflammasome activation. Moreover, it was suggested that exosomes might supply mitochondrial proteins to NP cells, and that the damaged mitochondria could be restored with this supplement. Further, in the rabbit IVDD model, exosomes significantly prevented the progression of degenerative changes. Our results confirmed that the NLRP3 inflammasome is an effective target for IVDD treatment and that the injection of exosomes could be a promising therapeutic strategy.

Keywords: Exosome; Intervertebral disc degeneration; Mitochondrion; NLRP3 inflammasome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Disease Progression
  • Exosomes / metabolism*
  • Hydrogen Peroxide / pharmacology
  • Inflammation / metabolism*
  • Intervertebral Disc Degeneration / metabolism
  • Intervertebral Disc Degeneration / therapy*
  • Lipid Bilayers / metabolism
  • Magnetic Resonance Imaging
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Nucleus Pulposus / metabolism*
  • Oxidants / metabolism*
  • Oxidative Stress
  • Oxygen / metabolism*
  • Proteomics
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Lipid Bilayers
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Nlrp3 protein, rat
  • Oxidants
  • Hydrogen Peroxide
  • Oxygen