Oct4-induced oligodendrocyte progenitor cells enhance functional recovery in spinal cord injury model.
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.
Hans Schöler Stem Cell Research Center (HSSCRC), School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea Max Planck Partner Group-Molecular Biomedicine Laboratory (MPPG-MBL), UNIST, Ulsan, South Korea jbkim@unist.ac.kr.
Jeong Beom
JB
Kim
Hans Schöler Stem Cell Research Center (HSSCRC), School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea Max Planck Partner Group-Molecular Biomedicine Laboratory (MPPG-MBL), UNIST, Ulsan, South Korea.
Hyunah
H
Lee
Group of Computational Biology and Bioinformatics, Biodonostia Health Research Institute, San Sebastián, Spain IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
Marcos J
MJ
Araúzo-Bravo
Department of Pediatrics and BK21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, South Korea.
Kyujin
K
Hwang
Hans Schöler Stem Cell Research Center (HSSCRC), School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea Max Planck Partner Group-Molecular Biomedicine Laboratory (MPPG-MBL), UNIST, Ulsan, South Korea.
Donggyu
D
Nam
Hans Schöler Stem Cell Research Center (HSSCRC), School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea Max Planck Partner Group-Molecular Biomedicine Laboratory (MPPG-MBL), UNIST, Ulsan, South Korea.
Myung Rae
MR
Park
Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
Holm
H
Zaehres
Department of Pediatrics and BK21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, South Korea.
Kook In
KI
Park
Hans Schöler Stem Cell Research Center (HSSCRC), School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea Max Planck Partner Group-Molecular Biomedicine Laboratory (MPPG-MBL), UNIST, Ulsan, South Korea.
Seok-Jin
SJ
Lee
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000166:cytology; D007150:Immunohistochemistry; D059785:Karyotype; D008297:Male; D051379:Mice; D016513:Mice, SCID; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D051381:Rats; D020127:Recovery of Function / Q000502:physiology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology
D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse
Oct4; direct conversion; myelination; oligodendrocyte progenitor cell; self‐renewal