title: Therapeutic potential of induced neural stem cells for spinal cord injury.
abstract: The spinal cord does not spontaneously regenerate, and treatment that ensures functional recovery after spinal cord injury (SCI) is still not available. Recently, fibroblasts have been directly converted into induced neural stem cells (iNSCs) by the forced expression defined transcription factors. Although directly converted iNSCs have been considered to be a cell source for clinical applications, their therapeutic potential has not yet been investigated. Here we show that iNSCs directly converted from mouse fibroblasts enhance the functional recovery of SCI animals. Engrafted iNSCs could differentiate into all neuronal lineages, including different subtypes of mature neurons. Furthermore, iNSC-derived neurons could form synapses with host neurons, thus enhancing the locomotor function recovery. A time course analysis of iNSC-treated SCI animals revealed that engrafted iNSCs effectively reduced the inflammatory response and apoptosis in the injured area. iNSC transplantation also promoted the active regeneration of the endogenous recipient environment in the absence of tumor formation. Therefore, our data suggest that directly converted iNSCs hold therapeutic potential for treatment of SCI and may thus represent a promising cell source for transplantation therapy in patients with SCI.
authors.affiliation: From the Department of Nanobiomedical Science and BK21PLUS NBM Global Research Center, Dankook University Graduate School, Cheonan 330714, Republic of Korea, the Institute of Tissue Regeneration Engineering, Dankook University, Cheonan 330714, Republic of Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Hong
authors.affiliation: the Departments of Stem Cell Biology and.
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Lee
authors.affiliation: the Departments of Stem Cell Biology and.
authors.forename: Seung Chan
authors.initials: SC
authors.lastname: Lee
authors.affiliation: From the Department of Nanobiomedical Science and BK21PLUS NBM Global Research Center, Dankook University Graduate School, Cheonan 330714, Republic of Korea, the Institute of Tissue Regeneration Engineering, Dankook University, Cheonan 330714, Republic of Korea.
authors.forename: Jong-Wan
authors.initials: JW
authors.lastname: Kim
authors.affiliation: the Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.
authors.forename: Kee-Pyo
authors.initials: KP
authors.lastname: Kim
authors.affiliation: the Departments of Stem Cell Biology and.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: the Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Tapia
authors.affiliation: the Departments of Stem Cell Biology and.
authors.forename: Kyung Tae
authors.initials: KT
authors.lastname: Lim
authors.affiliation: the Departments of Stem Cell Biology and.
authors.forename: Jonghun
authors.initials: J
authors.lastname: Kim
authors.affiliation: From the Department of Nanobiomedical Science and BK21PLUS NBM Global Research Center, Dankook University Graduate School, Cheonan 330714, Republic of Korea, the Institute of Tissue Regeneration Engineering, Dankook University, Cheonan 330714, Republic of Korea.
authors.forename: Hong-Sun
authors.initials: HS
authors.lastname: Ahn
authors.affiliation: the Departments of Stem Cell Biology and.
authors.forename: Kinarm
authors.initials: K
authors.lastname: Ko
authors.affiliation: Pharmacology, School of Medicine, and the Konkuk University Open-Innovation Center, Institute of Biomedical Science & Technology, Konkuk University, Gwangjin-gu, Seoul 143701, Republic of Korea.
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
authors.affiliation: the Departments of Stem Cell Biology and.
authors.forename: Hoon Taek
authors.initials: HT
authors.lastname: Lee
authors.affiliation: the Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany, the University of Münster, Medical Faculty, 48149 Münster, Germany, and.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
authors.affiliation: From the Department of Nanobiomedical Science and BK21PLUS NBM Global Research Center, Dankook University Graduate School, Cheonan 330714, Republic of Korea, the Institute of Tissue Regeneration Engineering, Dankook University, Cheonan 330714, Republic of Korea, the Department of Rehabilitation Medicine, College of Medicine, Dankook University, Cheonan 330714, Republic of Korea rhhyun@dankook.ac.kr.
authors.forename: Jung Keun
authors.initials: JK
authors.lastname: Hyun
authors.affiliation: the Departments of Stem Cell Biology and the Konkuk University Open-Innovation Center, Institute of Biomedical Science & Technology, Konkuk University, Gwangjin-gu, Seoul 143701, Republic of Korea, dwhan@konkuk.ac.kr.
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Han
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D019054:Evoked Potentials, Motor / Q000235:genetics / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000637:transplantation*; D008809:Mice, Inbred C3H; D008856:Microscopy, Fluorescence; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism / Q000637:transplantation*; D020411:Oligonucleotide Array Sequence Analysis; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy*; D013569:Synapses / Q000378:metabolism / Q000502:physiology
chemical_list: D064231:Nestin; D055748:SOXB1 Transcription Factors
keywords: Differentiation; Neural Stem Cell (NSC); Reprogramming; Stem Cells; Transplantation