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Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice

BACKGROUND: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease of the neuromuscular junction (NMJ), mostly associated with acetylcholine receptor (AChR) antibodies. Around 5–10 % of MG patients show antibodies to muscle-specific tyrosine kinase (MuSK). Mesenchymal stem cell (MSC) admi...

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Autores principales: Ulusoy, Canan, Zibandeh, Noushin, Yıldırım, Selin, Trakas, Nikolaos, Zisimopoulou, Paraskevi, Küçükerden, Melike, Tașlı, Hatice, Tzartos, Socrates, Göker, Kamil, Tüzün, Erdem, Akkoç, Tunç
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673854/
https://www.ncbi.nlm.nih.gov/pubmed/26646841
http://dx.doi.org/10.1186/s12974-015-0451-0
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author Ulusoy, Canan
Zibandeh, Noushin
Yıldırım, Selin
Trakas, Nikolaos
Zisimopoulou, Paraskevi
Küçükerden, Melike
Tașlı, Hatice
Tzartos, Socrates
Göker, Kamil
Tüzün, Erdem
Akkoç, Tunç
author_facet Ulusoy, Canan
Zibandeh, Noushin
Yıldırım, Selin
Trakas, Nikolaos
Zisimopoulou, Paraskevi
Küçükerden, Melike
Tașlı, Hatice
Tzartos, Socrates
Göker, Kamil
Tüzün, Erdem
Akkoç, Tunç
author_sort Ulusoy, Canan
collection PubMed
description BACKGROUND: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease of the neuromuscular junction (NMJ), mostly associated with acetylcholine receptor (AChR) antibodies. Around 5–10 % of MG patients show antibodies to muscle-specific tyrosine kinase (MuSK). Mesenchymal stem cell (MSC) administration has been shown to ameliorate muscle weakness in the experimental autoimmune myasthenia gravis (EAMG) model induced by AChR immunization. METHODS: To investigate the efficacy of stem cell treatment in MuSK-related EAMG, clinical and immunological features of MuSK-immunized mice with or without dental follicle MSC (DFMSC) treatment were compared. RESULTS: MuSK-immunized mice intravenously treated with DFMSC after second and third immunizations showed significantly lower EAMG incidence and severity and reduced serum anti-MuSK antibody, NMJ IgG, and C3 deposit levels and CD11b+ lymph node cell ratios. Moreover, lymph node cells of DFMSC-administered mice showed reduced proliferation and IL-6 and IL-12 production responses to MuSK stimulation. By contrast, proportions of B and T cell populations and production of a wide variety of cytokines were not affected from DFMSC treatment. CONCLUSIONS: Our results suggest that DFMSC treatment shows its beneficial effects mostly through suppression of innate immune system, whereas other immune functions appear to be preserved. Stem cell treatment might thus constitute a specific and effective treatment method in MuSK-associated MG. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0451-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-46738542015-12-10 Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice Ulusoy, Canan Zibandeh, Noushin Yıldırım, Selin Trakas, Nikolaos Zisimopoulou, Paraskevi Küçükerden, Melike Tașlı, Hatice Tzartos, Socrates Göker, Kamil Tüzün, Erdem Akkoç, Tunç J Neuroinflammation Research BACKGROUND: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease of the neuromuscular junction (NMJ), mostly associated with acetylcholine receptor (AChR) antibodies. Around 5–10 % of MG patients show antibodies to muscle-specific tyrosine kinase (MuSK). Mesenchymal stem cell (MSC) administration has been shown to ameliorate muscle weakness in the experimental autoimmune myasthenia gravis (EAMG) model induced by AChR immunization. METHODS: To investigate the efficacy of stem cell treatment in MuSK-related EAMG, clinical and immunological features of MuSK-immunized mice with or without dental follicle MSC (DFMSC) treatment were compared. RESULTS: MuSK-immunized mice intravenously treated with DFMSC after second and third immunizations showed significantly lower EAMG incidence and severity and reduced serum anti-MuSK antibody, NMJ IgG, and C3 deposit levels and CD11b+ lymph node cell ratios. Moreover, lymph node cells of DFMSC-administered mice showed reduced proliferation and IL-6 and IL-12 production responses to MuSK stimulation. By contrast, proportions of B and T cell populations and production of a wide variety of cytokines were not affected from DFMSC treatment. CONCLUSIONS: Our results suggest that DFMSC treatment shows its beneficial effects mostly through suppression of innate immune system, whereas other immune functions appear to be preserved. Stem cell treatment might thus constitute a specific and effective treatment method in MuSK-associated MG. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0451-0) contains supplementary material, which is available to authorized users. BioMed Central 2015-12-09 /pmc/articles/PMC4673854/ /pubmed/26646841 http://dx.doi.org/10.1186/s12974-015-0451-0 Text en © Ulusoy et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Ulusoy, Canan
Zibandeh, Noushin
Yıldırım, Selin
Trakas, Nikolaos
Zisimopoulou, Paraskevi
Küçükerden, Melike
Tașlı, Hatice
Tzartos, Socrates
Göker, Kamil
Tüzün, Erdem
Akkoç, Tunç
Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice
title Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice
title_full Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice
title_fullStr Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice
title_full_unstemmed Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice
title_short Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice
title_sort dental follicle mesenchymal stem cell administration ameliorates muscle weakness in musk-immunized mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673854/
https://www.ncbi.nlm.nih.gov/pubmed/26646841
http://dx.doi.org/10.1186/s12974-015-0451-0
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