Extracellular vesicles from human umbilical cord mesenchymal stem cells improve nerve regeneration after sciatic nerve transection in rats

J Cell Mol Med. 2019 Apr;23(4):2822-2835. doi: 10.1111/jcmm.14190. Epub 2019 Feb 17.

Abstract

Peripheral nerve injury results in limited nerve regeneration and severe functional impairment. Mesenchymal stem cells (MSCs) are a remarkable tool for peripheral nerve regeneration. The involvement of human umbilical cord MSC-derived extracellular vesicles (hUCMSC-EVs) in peripheral nerve regeneration, however, remains unknown. In this study, we evaluated functional recovery and nerve regeneration in rats that received hUCMSC-EV treatment after nerve transection. We observed that hUCMSC-EV treatment promoted the recovery of motor function and the regeneration of axons; increased the sciatic functional index; resulted in the generation of numerous axons and of several Schwann cells that surrounded individual axons; and attenuated the atrophy of the gastrocnemius muscle. hUCMSC-EVs aggregated to rat nerve defects, down-regulated interleukin (IL)-6 and IL-1β, up-regulated IL-10 and modulated inflammation in the injured nerve. These effects likely contributed to the promotion of nerve regeneration. Our findings indicate that hUCMSC-EVs can improve functional recovery and nerve regeneration by providing a favourable microenvironment for nerve regeneration. Thus, hUCMSC-EVs have considerable potential for application in the treatment of peripheral nerve injury.

Keywords: extracellular vesicles; human umbilical cord mesenchymal stem cell; improve; nerve regeneration; sciatic nerve transection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Extracellular Vesicles / transplantation*
  • Humans
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology*
  • Muscle, Skeletal / injuries
  • Muscular Atrophy / etiology
  • Muscular Atrophy / pathology
  • Muscular Atrophy / therapy
  • Nerve Regeneration*
  • Peripheral Nerve Injuries / etiology
  • Peripheral Nerve Injuries / pathology
  • Peripheral Nerve Injuries / therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Sciatic Nerve / injuries*
  • Sciatic Nerve / surgery
  • Umbilical Cord / cytology*