Exosomes from human adipose-derived stem cells promote sciatic nerve regeneration via optimizing Schwann cell function

J Cell Physiol. 2019 Dec;234(12):23097-23110. doi: 10.1002/jcp.28873. Epub 2019 May 23.

Abstract

Human adipose-derived stem cells (ASCs) have a potential for the treatment of peripheral nerve injury. Recent studies demonstrated that stem cells can mediate therapeutic effect by secreting exosomes. We aimed to investigate the effect of human ASCs derived exosomes (ASC-Exos) on peripheral nerve regeneration in vitro and in vivo. Our results showed after being internalized by Schwann cells (SCs), ASC-Exos significantly promoted SC proliferation, migration, myelination, and secretion of neurotrophic factors by upregulating corresponding genes in vitro. We next evaluated the efficacy of ASC-Exo therapy in a rat sciatic nerve transection model with a 10-mm gap. Axon regeneration, myelination, and restoration of denervation muscle atrophy in ASC-Exos treated group was significantly improved compared to vehicle control. This study demonstrates that ASC-Exos effectively promote peripheral nerve regeneration via optimizing SC function and thereby represent a novel therapeutic strategy for regenerative medicine and nerve tissue engineering.

Keywords: Schwann cells; exosomes; mesenchymal stem cells; nerve regeneration; peripheral nerve injuries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Axons / pathology
  • Cell Differentiation / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Exosomes / genetics*
  • Exosomes / transplantation
  • Humans
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Muscular Atrophy / genetics
  • Muscular Atrophy / pathology
  • Muscular Atrophy / therapy*
  • Nerve Fibers, Myelinated / metabolism
  • Nerve Regeneration / genetics*
  • Peripheral Nerve Injuries / genetics
  • Peripheral Nerve Injuries / pathology
  • Peripheral Nerve Injuries / therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / genetics
  • Schwann Cells / transplantation
  • Sciatic Nerve / growth & development
  • Sciatic Nerve / pathology