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Neural Progenitor-Like Cells Induced from Human Gingiva-Derived Mesenchymal Stem Cells Regulate Myelination of Schwann Cells in Rat Sciatic Nerve Regeneration

Authors
 Qunzhou Zhang  ;  Phuong Nguyen  ;  Qilin Xu  ;  Wonse Park  ;  Sumin Lee  ;  Akihiro Furuhashi  ;  Anh D. Le 
Citation
 STEM CELLS TRANSLATIONAL MEDICINE, Vol.6(2) : 458-470, 2017 
Journal Title
STEM CELLS TRANSLATIONAL MEDICINE
ISSN
 2157-6564 
Issue Date
2017
Keywords
Gingiva-derived mesenchymal stem cell ; Induced neural progenitor cells ; Myelination ; Peripheral nerve regeneration ; Schwann cells
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. Stem Cells Translational Medicine 2017;6:458-470.
Files in This Item:
T201702037.pdf Download
DOI
10.5966/sctm.2016-0177
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Advanced General Dentistry (통합치의학과) > 1. Journal Papers
Yonsei Authors
Park, Wonse(박원서) ORCID logo https://orcid.org/0000-0002-2081-1156
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154255
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