Effects of murine and human bone marrow-derived mesenchymal stem cells on cuprizone induced demyelination
For the treatment of patients with multiple sclerosis there are no regenerative approaches to enhance remyelination. Mesenchymal stem cells (MSC) have been proposed to exert such regenerative functions. Intravenous administration of human MSC reduced the clinical severity of experimental autoimmune...
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| creator | Nessler, Jasmin Bénardais, Karelle Gudi, Viktoria Hoffmann, Andrea Salinas Tejedor, Laura Janßen, Stefanie Prajeeth, Chittappen Kandiyil Baumgärtner, Wolfgang Kavelaars, Annemieke Heijnen, Cobi J van Velthoven, Cindy Hansmann, Florian Skripuletz, Thomas Stangel, Martin |
| description | For the treatment of patients with multiple sclerosis there are no regenerative approaches to enhance remyelination. Mesenchymal stem cells (MSC) have been proposed to exert such regenerative functions. Intravenous administration of human MSC reduced the clinical severity of experimental autoimmune encephalomyelitis (EAE), an animal model mimicking some aspects of multiple sclerosis. However, it is not clear if this effect was achieved by systemic immunomodulation or if there is an active neuroregeneration in the central nervous system (CNS). In order to investigate remyelination and regeneration in the CNS we analysed the effects of intravenously and intranasally applied murine and human bone marrow-derived MSC on cuprizone induced demyelination, a toxic animal model which allows analysis of remyelination without the influence of the peripheral immune system. In contrast to EAE no effects of MSC on de- and remyelination and glial cell reactions were found. In addition, neither murine nor human MSC entered the lesions in the CNS in this toxic model. In conclusion, MSC are not directed into CNS lesions in the cuprizone model where the blood-brain-barrier is intact and thus cannot provide support for regenerative processes. |
| doi_str_mv | 10.1371/journal.pone.0069795 |
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Mesenchymal stem cells (MSC) have been proposed to exert such regenerative functions. Intravenous administration of human MSC reduced the clinical severity of experimental autoimmune encephalomyelitis (EAE), an animal model mimicking some aspects of multiple sclerosis. However, it is not clear if this effect was achieved by systemic immunomodulation or if there is an active neuroregeneration in the central nervous system (CNS). In order to investigate remyelination and regeneration in the CNS we analysed the effects of intravenously and intranasally applied murine and human bone marrow-derived MSC on cuprizone induced demyelination, a toxic animal model which allows analysis of remyelination without the influence of the peripheral immune system. In contrast to EAE no effects of MSC on de- and remyelination and glial cell reactions were found. In addition, neither murine nor human MSC entered the lesions in the CNS in this toxic model. In conclusion, MSC are not directed into CNS lesions in the cuprizone model where the blood-brain-barrier is intact and thus cannot provide support for regenerative processes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0069795</identifier><identifier>PMID: 23922802</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Biology ; Bone marrow ; Bone Marrow Cells - cytology ; Brain ; Brain research ; Cell Count ; Cell culture ; Cell Tracking ; Central nervous system ; Chemokines - genetics ; Chemokines - metabolism ; Corpus Callosum - metabolism ; Corpus Callosum - pathology ; Cuprizone ; Cytoprotection ; Demyelinating Diseases - chemically induced ; Demyelinating Diseases - pathology ; Demyelinating Diseases - therapy ; Demyelination ; Experimental allergic encephalomyelitis ; Feeding Behavior ; Gene expression ; Glial cells ; Growth factors ; Hepatocyte Growth Factor - genetics ; Hepatocyte Growth Factor - metabolism ; Humans ; Immune system ; Immunohistochemistry ; Immunomodulation ; Integrin alpha4 - metabolism ; Intravenous administration ; Laboratories ; Lesions ; Male ; Medical schools ; Medicine ; Mesenchymal Stem Cell Transplantation ; Mesenchymal stem cells ; Mesenchymal Stem Cells - cytology ; Mesenchyme ; Mice ; Mice, Inbred C57BL ; Mimicry ; Multiple sclerosis ; Myelination ; Neurology ; Neurosciences ; Oligodendroglia - metabolism ; Oligodendroglia - pathology ; Organic Chemicals - metabolism ; Penicillin ; Regeneration ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Spinal cord ; Stem cell transplantation ; Stem cells ; Veterinary medicine</subject><ispartof>PloS one, 2013-07, Vol.8 (7), p.e69795</ispartof><rights>2013 Nessler et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Mesenchymal stem cells (MSC) have been proposed to exert such regenerative functions. Intravenous administration of human MSC reduced the clinical severity of experimental autoimmune encephalomyelitis (EAE), an animal model mimicking some aspects of multiple sclerosis. However, it is not clear if this effect was achieved by systemic immunomodulation or if there is an active neuroregeneration in the central nervous system (CNS). In order to investigate remyelination and regeneration in the CNS we analysed the effects of intravenously and intranasally applied murine and human bone marrow-derived MSC on cuprizone induced demyelination, a toxic animal model which allows analysis of remyelination without the influence of the peripheral immune system. In contrast to EAE no effects of MSC on de- and remyelination and glial cell reactions were found. In addition, neither murine nor human MSC entered the lesions in the CNS in this toxic model. In conclusion, MSC are not directed into CNS lesions in the cuprizone model where the blood-brain-barrier is intact and thus cannot provide support for regenerative processes.</description><subject>Animals</subject><subject>Biology</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells - cytology</subject><subject>Brain</subject><subject>Brain research</subject><subject>Cell Count</subject><subject>Cell culture</subject><subject>Cell Tracking</subject><subject>Central nervous system</subject><subject>Chemokines - genetics</subject><subject>Chemokines - metabolism</subject><subject>Corpus Callosum - metabolism</subject><subject>Corpus Callosum - pathology</subject><subject>Cuprizone</subject><subject>Cytoprotection</subject><subject>Demyelinating Diseases - chemically induced</subject><subject>Demyelinating Diseases - pathology</subject><subject>Demyelinating Diseases - therapy</subject><subject>Demyelination</subject><subject>Experimental allergic encephalomyelitis</subject><subject>Feeding Behavior</subject><subject>Gene expression</subject><subject>Glial cells</subject><subject>Growth factors</subject><subject>Hepatocyte Growth Factor - 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Mesenchymal stem cells (MSC) have been proposed to exert such regenerative functions. Intravenous administration of human MSC reduced the clinical severity of experimental autoimmune encephalomyelitis (EAE), an animal model mimicking some aspects of multiple sclerosis. However, it is not clear if this effect was achieved by systemic immunomodulation or if there is an active neuroregeneration in the central nervous system (CNS). In order to investigate remyelination and regeneration in the CNS we analysed the effects of intravenously and intranasally applied murine and human bone marrow-derived MSC on cuprizone induced demyelination, a toxic animal model which allows analysis of remyelination without the influence of the peripheral immune system. In contrast to EAE no effects of MSC on de- and remyelination and glial cell reactions were found. In addition, neither murine nor human MSC entered the lesions in the CNS in this toxic model. In conclusion, MSC are not directed into CNS lesions in the cuprizone model where the blood-brain-barrier is intact and thus cannot provide support for regenerative processes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23922802</pmid><doi>10.1371/journal.pone.0069795</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1428143595 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Biology Bone marrow Bone Marrow Cells - cytology Brain Brain research Cell Count Cell culture Cell Tracking Central nervous system Chemokines - genetics Chemokines - metabolism Corpus Callosum - metabolism Corpus Callosum - pathology Cuprizone Cytoprotection Demyelinating Diseases - chemically induced Demyelinating Diseases - pathology Demyelinating Diseases - therapy Demyelination Experimental allergic encephalomyelitis Feeding Behavior Gene expression Glial cells Growth factors Hepatocyte Growth Factor - genetics Hepatocyte Growth Factor - metabolism Humans Immune system Immunohistochemistry Immunomodulation Integrin alpha4 - metabolism Intravenous administration Laboratories Lesions Male Medical schools Medicine Mesenchymal Stem Cell Transplantation Mesenchymal stem cells Mesenchymal Stem Cells - cytology Mesenchyme Mice Mice, Inbred C57BL Mimicry Multiple sclerosis Myelination Neurology Neurosciences Oligodendroglia - metabolism Oligodendroglia - pathology Organic Chemicals - metabolism Penicillin Regeneration RNA, Messenger - genetics RNA, Messenger - metabolism Spinal cord Stem cell transplantation Stem cells Veterinary medicine |
| title | Effects of murine and human bone marrow-derived mesenchymal stem cells on cuprizone induced demyelination |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T02%3A17%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effects%20of%20murine%20and%20human%20bone%20marrow-derived%20mesenchymal%20stem%20cells%20on%20cuprizone%20induced%20demyelination&rft.jtitle=PloS%20one&rft.au=Nessler,%20Jasmin&rft.date=2013-07-26&rft.volume=8&rft.issue=7&rft.spage=e69795&rft.pages=e69795-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0069795&rft_dat=%3Cproquest_plos_%3E3054536251%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1428143595&rft_id=info:pmid/23922802&rft_doaj_id=oai_doaj_org_article_6c82af381cb14b338c98c306b4bc641e&rfr_iscdi=true |