Effect of exosomes from adipose-derived stem cells on the apoptosis of Schwann cells in peripheral nerve injury

CNS Neurosci Ther. 2020 Feb;26(2):189-196. doi: 10.1111/cns.13187. Epub 2019 Jul 6.

Abstract

Aims: Recovery after peripheral nerve injury (PNI) is often difficult, and there is no optimal treatment. Schwann cells (SCs) are important for peripheral nerve regeneration, so SC-targeting treatments have gained importance. Adipose-derived stem cells (ADSCs) and their exosomes can promote peripheral nerve repair, but their interactions with SCs are unclear.

Methods: Purified SCs from sciatic nerve injury sites were harvested, and apoptosis and proliferation of SCs at post-PNI 24 hours were analyzed. The effects of coculture with ADSCs and different concentrations of ADSC-derived exosomes (ADSC-Exo) were studied through in vitro experiments by flow cytometry, CCK8 assay, immunofluorescence staining, and histological analysis. The expression of the apoptosis-related genes Bcl-2 and Bax was also analyzed by qRT-PCR.

Results: ADSC-Exo reduced the apoptosis of SCs after PNI by upregulating the anti-apoptotic Bcl-2 mRNA expression and downregulating the pro-apoptotic Bax mRNA expression. Further, it also improved the proliferation rate of SCs. This effect was confirmed by the morphological and histological findings in PNI model rats.

Conclusion: Our results present a novel exosome-mediated mechanism for ADSC-SC cross talk that reduces the apoptosis and promotes the proliferation of SCs and may have therapeutic potential in the future.

Keywords: Schwann cells; adipose-derived stem cells; apoptosis; exosomes; peripheral nerve injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Apoptosis*
  • Cell Proliferation
  • Coculture Techniques
  • Exosomes*
  • Male
  • Nerve Regeneration
  • Peripheral Nerve Injuries / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Wistar
  • Schwann Cells / pathology*
  • Sciatic Nerve / injuries
  • Stem Cells*
  • bcl-2-Associated X Protein / genetics

Substances

  • Bax protein, rat
  • Bcl2 protein, rat
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-2-Associated X Protein