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Potential of Adult Endogenous Neural Stem/Progenitor Cells in the Spinal Cord to Contribute to Remyelination in Experimental Autoimmune Encephalomyelitis
Demyelination and remyelination play pivotal roles in the pathological process of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), a well-established animal model of MS. Although increasing evidence shows that various stimuli can promote the activation/induction of endoge...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769975/ https://www.ncbi.nlm.nih.gov/pubmed/31484369 http://dx.doi.org/10.3390/cells8091025 |
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author | Maeda, Yuki Nakagomi, Nami Nakano-Doi, Akiko Ishikawa, Hiroto Tatsumi, Yoshiki Bando, Yoshio Yoshikawa, Hiroo Matsuyama, Tomohiro Gomi, Fumi Nakagomi, Takayuki |
author_facet | Maeda, Yuki Nakagomi, Nami Nakano-Doi, Akiko Ishikawa, Hiroto Tatsumi, Yoshiki Bando, Yoshio Yoshikawa, Hiroo Matsuyama, Tomohiro Gomi, Fumi Nakagomi, Takayuki |
author_sort | Maeda, Yuki |
collection | PubMed |
description | Demyelination and remyelination play pivotal roles in the pathological process of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), a well-established animal model of MS. Although increasing evidence shows that various stimuli can promote the activation/induction of endogenous neural stem/progenitor cells (NSPCs) in the central nervous system, the potential contributions of these cells to remyelination following inflammatory injury remain to be fully investigated. In the present study, using an adult mouse model of EAE induced by myelin oligodendrocyte glycoprotein (MOG) peptide, we investigated whether adult NSPCs in the spinal cord can lead to remyelination under inflammatory conditions. Immunohistochemistry showed that cells expressing the NSPC marker Nestin appeared after MOG peptide administration, predominantly at the sites of demyelination where abundant inflammatory cells had accumulated, whereas Nestin(+) cells were rarely present in the spinal cord of PBS-treated control mice. In vitro, Nestin(+) NSPCs obtained from EAE mice spinal cords could differentiate into multiple neural lineages, including neurons, astrocytes, and myelin-producing oligodendrocytes. Using the Cre–LoxP system, we established a mouse strain expressing yellow fluorescent protein (YFP) under the control of the Nestin promoter and investigated the expression patterns of YFP-expressing cells in the spinal cord after EAE induction. At the chronic phase of the disease, immunohistochemistry showed that YFP(+) cells in the injured regions expressed markers for various neural lineages, including myelin-forming oligodendrocytes. These results show that adult endogenous NSPCs in the spinal cord can be subject to remyelination under inflammatory conditions, such as after EAE, suggesting that endogenous NSPCs represent a therapeutic target for MS treatment. |
format | Online Article Text |
id | pubmed-6769975 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67699752019-10-30 Potential of Adult Endogenous Neural Stem/Progenitor Cells in the Spinal Cord to Contribute to Remyelination in Experimental Autoimmune Encephalomyelitis Maeda, Yuki Nakagomi, Nami Nakano-Doi, Akiko Ishikawa, Hiroto Tatsumi, Yoshiki Bando, Yoshio Yoshikawa, Hiroo Matsuyama, Tomohiro Gomi, Fumi Nakagomi, Takayuki Cells Article Demyelination and remyelination play pivotal roles in the pathological process of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), a well-established animal model of MS. Although increasing evidence shows that various stimuli can promote the activation/induction of endogenous neural stem/progenitor cells (NSPCs) in the central nervous system, the potential contributions of these cells to remyelination following inflammatory injury remain to be fully investigated. In the present study, using an adult mouse model of EAE induced by myelin oligodendrocyte glycoprotein (MOG) peptide, we investigated whether adult NSPCs in the spinal cord can lead to remyelination under inflammatory conditions. Immunohistochemistry showed that cells expressing the NSPC marker Nestin appeared after MOG peptide administration, predominantly at the sites of demyelination where abundant inflammatory cells had accumulated, whereas Nestin(+) cells were rarely present in the spinal cord of PBS-treated control mice. In vitro, Nestin(+) NSPCs obtained from EAE mice spinal cords could differentiate into multiple neural lineages, including neurons, astrocytes, and myelin-producing oligodendrocytes. Using the Cre–LoxP system, we established a mouse strain expressing yellow fluorescent protein (YFP) under the control of the Nestin promoter and investigated the expression patterns of YFP-expressing cells in the spinal cord after EAE induction. At the chronic phase of the disease, immunohistochemistry showed that YFP(+) cells in the injured regions expressed markers for various neural lineages, including myelin-forming oligodendrocytes. These results show that adult endogenous NSPCs in the spinal cord can be subject to remyelination under inflammatory conditions, such as after EAE, suggesting that endogenous NSPCs represent a therapeutic target for MS treatment. MDPI 2019-09-03 /pmc/articles/PMC6769975/ /pubmed/31484369 http://dx.doi.org/10.3390/cells8091025 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Maeda, Yuki Nakagomi, Nami Nakano-Doi, Akiko Ishikawa, Hiroto Tatsumi, Yoshiki Bando, Yoshio Yoshikawa, Hiroo Matsuyama, Tomohiro Gomi, Fumi Nakagomi, Takayuki Potential of Adult Endogenous Neural Stem/Progenitor Cells in the Spinal Cord to Contribute to Remyelination in Experimental Autoimmune Encephalomyelitis |
title | Potential of Adult Endogenous Neural Stem/Progenitor Cells in the Spinal Cord to Contribute to Remyelination in Experimental Autoimmune Encephalomyelitis |
title_full | Potential of Adult Endogenous Neural Stem/Progenitor Cells in the Spinal Cord to Contribute to Remyelination in Experimental Autoimmune Encephalomyelitis |
title_fullStr | Potential of Adult Endogenous Neural Stem/Progenitor Cells in the Spinal Cord to Contribute to Remyelination in Experimental Autoimmune Encephalomyelitis |
title_full_unstemmed | Potential of Adult Endogenous Neural Stem/Progenitor Cells in the Spinal Cord to Contribute to Remyelination in Experimental Autoimmune Encephalomyelitis |
title_short | Potential of Adult Endogenous Neural Stem/Progenitor Cells in the Spinal Cord to Contribute to Remyelination in Experimental Autoimmune Encephalomyelitis |
title_sort | potential of adult endogenous neural stem/progenitor cells in the spinal cord to contribute to remyelination in experimental autoimmune encephalomyelitis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769975/ https://www.ncbi.nlm.nih.gov/pubmed/31484369 http://dx.doi.org/10.3390/cells8091025 |
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