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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
Affiliation:1. Hans Sch?ler Stem Cell Research Center (HSSCRC), School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea;2. Max Planck Partner Group‐Molecular Biomedicine Laboratory (MPPG‐MBL), UNIST, Ulsan, South Korea;3. Group of Computational Biology and Bioinformatics, Biodonostia Health Research Institute, San Sebastián, Spain;4. IKERBASQUE, Basque Foundation for Science, Bilbao, Spain;5. Department of Pediatrics and BK21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, South Korea;6. Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany
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.
Keywords:direct conversion  myelination     Oct4     oligodendrocyte progenitor cell  self‐renewal
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