The Combination of Adipose-derived Schwann-like Cells and Acellular Nerve Allografts Promotes Sciatic Nerve Regeneration and Repair through the JAK2/STAT3 Signaling Pathway in Rats

Neuroscience. 2019 Dec 1:422:134-145. doi: 10.1016/j.neuroscience.2019.10.018. Epub 2019 Nov 1.

Abstract

Schwann cells (SCs) combined with acellular nerve allografts (ANAs) effectively promote the regeneration and repair of peripheral nerves, but the exact mechanism has not been fully elucidated. However, the disadvantages of SCs include their limited source and slow rate of expansion in vitro. Previous studies have found that adipose-derived stem cells have the ability to differentiate into Schwann-like cells. Therefore, we speculated that Schwann-like cells combined with ANAs could profoundly facilitate nerve regeneration and repair. The aim of the present study was to investigate the cellular and molecular mechanisms of regeneration and repair. In this study, tissue-engineered nerves were first constructed by adipose-derived Schwann-like cells and ANAs to bridge missing sciatic nerves. Then, the rats were randomly divided into five groups (n = 12 per group): a Control group; a Model group; an ADSC group; an SC-L group; and a DMEM group. Twelve weeks postsurgery, behavioral function tests and molecular biological techniques were used to evaluate the function of regenerated nerves and the relevant molecular mechanisms after sciatic nerve injury (SNI). The results showed that adipose-derived Schwann-like cells combined with ANAs markedly promoted sciatic nerve regeneration and repair. These findings also demonstrated that the expression of neurotrophic factors (NFs) was increased, and the expression of Janus activated kinase2 (JAK2)/P-JAK2, signal transducer and activator of transcription-3 (STAT3)/P-STAT3 was decreased in the spinal cord after SNI. Therefore, these results suggested that highly expressed NFs in the spinal cord could promote nerve regeneration and repair by inhibiting activation of the JAK2/STAT3 signaling pathway.

Keywords: JAK2/STAT3; Schwann-like cells; acellular nerve allografts; adipose-derived stem cells; regeneration and repair; sciatic nerve injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allografts / transplantation*
  • Animals
  • Brain-Derived Neurotrophic Factor / biosynthesis
  • Ciliary Neurotrophic Factor / biosynthesis
  • Janus Kinase 2 / physiology*
  • Male
  • Mesenchymal Stem Cell Transplantation / methods
  • Nerve Growth Factor / biosynthesis
  • Nerve Regeneration / physiology*
  • Neurons / transplantation
  • Rats
  • Recovery of Function / physiology
  • STAT3 Transcription Factor / physiology*
  • Sciatic Nerve / injuries
  • Sciatic Nerve / physiopathology*
  • Sciatic Nerve / surgery
  • Signal Transduction / physiology
  • Spinal Cord / metabolism

Substances

  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • Ciliary Neurotrophic Factor
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Nerve Growth Factor
  • Jak2 protein, rat
  • Janus Kinase 2