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2092-64134972017Jul28Experimental & molecular medicineExp Mol MedRapid generation of OPC-like cells from human pluripotent stem cells for treating spinal cord injury.e361e36110.1038/emm.2017.106Remyelination via the transplantation of oligodendrocyte precursor cells (OPCs) has been considered as a strategy to improve the locomotor deficits caused by traumatic spinal cord injury (SCI). To date, enormous efforts have been made to derive OPCs from human pluripotent stem cells (hPSCs), and significant progress in the transplantation of such cells in SCI animal models has been reported. The current methods generally require a long period of time (>2 months) to obtain transplantable OPCs, which hampers their clinical utility for patients with SCI. Here we demonstrate a rapid and efficient method to differentiate hPSCs into neural progenitors that retain the features of OPCs (referred to as OPC-like cells). We used cell sorting to select A2B5-positive cells from hPSC-derived neural rosettes and cultured the selected cells in the presence of signaling cues, including sonic hedgehog, PDGF and insulin-like growth factor-1. This method robustly generated neural cells positive for platelet-derived growth factor receptor-α (PDGFRα) and NG2 (~90%) after 4 weeks of differentiation. Behavioral tests revealed that the transplantation of the OPC-like cells into the spinal cords of rats with contusive SCI at the thoracic level significantly improved hindlimb locomotor function. Electrophysiological assessment revealed enhanced neural conduction through the injury site. Histological examination showed increased numbers of axon with myelination at the injury site and graft-derived myelin formation with no evidence of tumor formation. Our method provides a cell source from hPSCs that has the potential to recover motor function following SCI.KimDae-SungDSDepartment of Biotechnology and BK21 PLUS project for Biotechnology, Korea University, Seoul, Republic of Korea.Institute of Animal Molecular Biotechnology, Korea University, Seoul, Republic of Korea.Department of Pediatrics, Korea University Guro Hospital, Seoul, Republic of Korea.JungSe JungSJDepartment of Physiology, Yonsei University College of Medicine, Seoul, Republic of Korea.LeeJae SoukJSDepartment of Physiology, Yonsei University College of Medicine, Seoul, Republic of Korea.BK21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.LimBo YoungBYDepartment of Physiology, Yonsei University College of Medicine, Seoul, Republic of Korea.KimHyun AhHADepartment of Physiology, Yonsei University College of Medicine, Seoul, Republic of Korea.YooJeong-EunJEDepartment of Physiology, Yonsei University College of Medicine, Seoul, Republic of Korea.BK21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.KimDong-WookDWDepartment of Physiology, Yonsei University College of Medicine, Seoul, Republic of Korea.BK21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.LeemJoong WooJWDepartment of Physiology, Yonsei University College of Medicine, Seoul, Republic of Korea.engJournal ArticleResearch Support, Non-U.S. Gov't20170728
United StatesExp Mol Med96078801226-36130Antigens0Proteoglycans0chondroitin sulfate proteoglycan 4EC 2.7.10.1Receptor, Platelet-Derived Growth Factor alphaIMAnimalsAntigensmetabolismAxonsmetabolismBehavior Rating ScaleCell DifferentiationCell LineCells, CulturedDisease Models, AnimalHindlimbHumansMaleMyelin SheathphysiologyOligodendrocyte Precursor CellscytologytransplantationPluripotent Stem CellscytologytransplantationProteoglycansmetabolismRatsRats, Sprague-DawleyReceptor, Platelet-Derived Growth Factor alphametabolismSpinal Cord InjuriessurgeryTime FactorsThe authors declare no conflict of interest.20161052017272017214201772960201772960201841460201771epublish28751784PMC556595210.1038/emm.2017.106emm2017106Noble M, Mayer-Pröschel M, Davies JE, Davies SJ, Pröschel C. Cell therapies for the central nervous system: how do we identify the best candidates? Curr Opin Neurol 2011; 24: 570–576.22027545Fawcett JW, Asher RA. The glial scar and central nervous system repair. 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