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Oct4-induced oligodendrocyte progenitor cells enhance functional recovery in spinal cord injury model

Authors
 Jeong Beom Kim  ;  Hyunah Lee  ;  Marcos J Araúzo-Bravo  ;  Kyujin Hwang  ;  Donggyu Nam  ;  Myung Rae Park  ;  Holm Zaehres  ;  Kook In Park  ;  Seok-Jin Lee 
Citation
 EMBO JOURNAL, Vol.34(23) : 2971-2983, 2015 
Journal Title
EMBO JOURNAL
ISSN
 0261-4189 
Issue Date
2015
MeSH
Animals ; Cells, Cultured ; Disease Models, Animal ; Fibroblasts/cytology ; Immunohistochemistry ; Karyotype ; Male ; Mice ; Mice, SCID ; Octamer Transcription Factor-3/genetics ; Octamer Transcription Factor-3/metabolism* ; Oligodendroglia/cytology ; Oligodendroglia/metabolism* ; Oligodendroglia/physiology* ; Rats ; Recovery of Function/physiology ; Spinal Cord Injuries/genetics ; Spinal Cord Injuries/metabolism* ; Spinal Cord Injuries/therapy* ; Stem Cell Transplantation ; Stem Cells/cytology ; Stem Cells/metabolism* ; Stem Cells/physiology
Keywords
Oct4 ; direct conversion ; myelination ; oligodendrocyte progenitor cell ; self‐renewal
Abstract
The generation of patient-specific oligodendrocyte progenitor cells (OPCs) holds great potential as an expandable cell source for cell replacement therapy as well as drug screening in spinal cord injury or demyelinating diseases. Here, we demonstrate that induced OPCs (iOPCs) can be directly derived from adult mouse fibroblasts by Oct4-mediated direct reprogramming, using anchorage-independent growth to ensure high purity. Homogeneous iOPCs exhibit typical small-bipolar morphology, maintain their self-renewal capacity and OPC marker expression for more than 31 passages, share high similarity in the global gene expression profile to wild-type OPCs, and give rise to mature oligodendrocytes and astrocytes in vitro and in vivo. Notably, transplanted iOPCs contribute to functional recovery in a spinal cord injury (SCI) model without tumor formation. This study provides a simple strategy to generate functional self-renewing iOPCs and yields insights for the in-depth study of demyelination and regenerative medicine.
Files in This Item:
T201504978.pdf Download
DOI
10.15252/embj.201592652
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Park, Kook In(박국인) ORCID logo https://orcid.org/0000-0001-8499-9293
Hwang, Kyujin(황규진) ORCID logo https://orcid.org/0000-0001-5193-5154
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/156965
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