Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Improves Spinal Cord Function After Injury in Rats by Activating Autophagy

Drug Des Devel Ther. 2020 Apr 29:14:1621-1631. doi: 10.2147/DDDT.S237502. eCollection 2020.

Abstract

Background: Spinal cord injury (SCI) is a global medical problem. The smallest membrane-bound nanovesicles, known as exosomes, have a role in complex intercellular communication systems and can be used directly as therapeutic agents by acting as important paracrine factors. Nevertheless, the use of exosomes derived from BMSCs (BMSC-Exos) to treat SCI has been less, and the specific mechanism has not yet been reported.

Methods: BMSC-Exos were characterized by TEM, NTA and Western blot. The effects of BMSC-Exos treatment were compared by SCI in vivo model and a series of in vitro experiments.

Results: BMSC-Exos were found to enhance the expression of autophagy-related proteins LC3IIB and Beclin-1 and enabled autophagosomes formation. After BMSC-Exos treatment, there was marked decline in the level of expression of proapoptotic protein cleaved caspase-3, while that of the antiapoptotic protein Bcl-2 was upregulated.

Conclusion: BMSC-Exos can attenuate neuronal apoptosis by promoting autophagy and promote the potential efficacy of functional behavior recovery in SCI rats. In summary, these findings expand the theoretical knowledge and forms a realistic route for the future treatment of SCI by BMSC-Exos.

Keywords: apoptosis; autophagy; bone marrow mesenchymal stem cells; exosomes; spinal cord injury.

MeSH terms

  • Animals
  • Autophagy*
  • Bone Marrow / metabolism*
  • Disease Models, Animal
  • Exosomes / metabolism*
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries / metabolism*

Substances

  • Bcl2 protein, rat
  • Proto-Oncogene Proteins c-bcl-2