Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version

2-2017

Publication Source

Stem cells translational medicine

Volume

6

Issue

2

Start Page

458

Last Page

470

DOI

10.5966/sctm.2016-0177

Abstract

Regeneration of peripheral nerve injury remains a major clinical challenge. Recently, mesenchymal stem cells (MSCs) have been considered as potential candidates for peripheral nerve regeneration; however, the underlying mechanisms remain elusive. Here, we show that human gingiva-derived MSCs (GMSCs) could be directly induced into multipotent NPCs (iNPCs) under minimally manipulated conditions without the introduction of exogenous genes. Using a crush-injury model of rat sciatic nerve, we demonstrate that GMSCs transplanted to the injury site could differentiate into neuronal cells, whereas iNPCs could differentiate into both neuronal and Schwann cells. After crush injury, iNPCs, compared with GMSCs, displayed superior therapeutic effects on axonal regeneration at both the injury site and the distal segment of the injured sciatic nerve. Mechanistically, transplantation of GMSCs, especially iNPCs, significantly attenuated injury-triggered increase in the expression of c-Jun, a transcription factor that functions as a major negative regulator of myelination and plays a central role in dedifferentiation/reprogramming of Schwann cells into a progenitor-like state. Meanwhile, our results also demonstrate that transplantation of GMSCs and iNPCs consistently increased the expression of Krox-20/EGR2, a transcription factor that governs the expression of myelin proteins and facilitates myelination. Altogether, our findings suggest that transplantation of GMSCs and iNPCs promotes peripheral nerve repair/regeneration, possibly by promoting remyelination of Schwann cells mediated via the regulation of the antagonistic myelination regulators, c-Jun and Krox-20/EGR2. © AlphaMed Press, 2016 The Authors.

Keywords

Gingiva-derived mesenchymal stem cell, Induced neural progenitor cells, Myelination, Peripheral nerve regeneration, Schwann cells, Animals, Cell Differentiation, Cell Separation, Cells, Cultured, Crush Injuries, Disease Models, Animal, Early Growth Response Protein 2, Female, Gingiva, Humans, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells, Myelin Sheath, Neural Stem Cells, Phenotype, Proto-Oncogene Proteins c-jun, Rats, Sprague-Dawley, Remyelination, Schwann Cells, Sciatic Nerve, Sciatic Neuropathy, Signal Transduction, brain derived neurotrophic factor, early growth response factor 2, interleukin 6, myelin protein, nerve growth factor beta subunit, nestin, neurotrophin 3, protein c jun, protein S 100, transcription factor PAX6, transcription factor Sox1, tubulin, vasculotropin, vimentin, early growth response factor 2, EGR2 protein, human, protein c jun, animal model, animal tissue, Article, controlled study, enzyme linked immunosorbent assay, experimental sciatic nerve injury, female, flow cytometry, fluorescence microscopy, gene expression, gingiva, human, human tissue, immunohistochemistry, mesenchymal stem cell, multipotent stem cell, myelination, nerve cell differentiation, nerve regeneration, neural stem cell, nonhuman, nuclear reprogramming, protein expression, rat, Schwann cell, stem cell transplantation, Western blotting, animal, cell culture, cell differentiation, cell separation, comparative study, crush trauma, cytology, disease model, gingiva, mesenchymal stem cell, mesenchymal stem cell transplantation, metabolism, myelin sheath, neural stem cell, pathology, pathophysiology, phenotype, remyelinization, Schwann cell, sciatic nerve, sciatic neuropathy, signal transduction, Sprague Dawley rat, transplantation

Download

Share

COinS
 

Date Posted: 10 February 2023

This document has been peer reviewed.