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J Biol Chem. 2014 Nov 21;289(47):32512-25. doi: 10.1074/jbc.M114.588871. Epub 2014 Oct 6.

Therapeutic potential of induced neural stem cells for spinal cord injury.

Author information

1
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.
2
the Departments of Stem Cell Biology and.
3
the Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.
4
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.
5
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.
6
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.
7
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.

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.

KEYWORDS:

Differentiation; Neural Stem Cell (NSC); Reprogramming; Stem Cells; Transplantation

PMID:
25294882
PMCID:
PMC4239606
DOI:
10.1074/jbc.M114.588871
[Indexed for MEDLINE]
Free PMC Article

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