Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice
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 h...
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| Veröffentlicht in: | Journal of neuroinflammation 2015-12, Vol.12 (1), p.231-231, Article 231 |
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| creator | Ulusoy, Canan Zibandeh, Noushin Yıldırım, Selin Trakas, Nikolaos Zisimopoulou, Paraskevi Küçükerden, Melike Tașlı, Hatice Tzartos, Socrates Göker, Kamil Tüzün, Erdem Akkoç, Tunç |
| description | 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.
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.
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.
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. |
| doi_str_mv | 10.1186/s12974-015-0451-0 |
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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.
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.
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.</description><identifier>ISSN: 1742-2094</identifier><identifier>EISSN: 1742-2094</identifier><identifier>DOI: 10.1186/s12974-015-0451-0</identifier><identifier>PMID: 26646841</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Animals ; Autoimmunity ; Cells, Cultured ; Dendritic cells ; Dental Sac - cytology ; Dental Sac - immunology ; Dental Sac - transplantation ; Female ; Humans ; Immunization - methods ; Immunoglobulin G ; Mesenchymal Stem Cell Transplantation - methods ; Mesenchymal Stromal Cells - immunology ; Mice ; Mice, Inbred C57BL ; Muscle weakness ; Muscle Weakness - immunology ; Muscle Weakness - therapy ; Myasthenia gravis ; Receptor Protein-Tyrosine Kinases - administration & dosage ; Receptor Protein-Tyrosine Kinases - immunology ; Receptors, Cholinergic - administration & dosage ; Receptors, Cholinergic - immunology ; Stem cells ; T cells ; Tyrosine</subject><ispartof>Journal of neuroinflammation, 2015-12, Vol.12 (1), p.231-231, Article 231</ispartof><rights>COPYRIGHT 2015 BioMed Central Ltd.</rights><rights>Ulusoy et al. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c466t-6d810745093e2d54a2abf4529c8369076a35a03d0797f54999ca8b4d208632bb3</citedby><cites>FETCH-LOGICAL-c466t-6d810745093e2d54a2abf4529c8369076a35a03d0797f54999ca8b4d208632bb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673854/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673854/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26646841$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ulusoy, Canan</creatorcontrib><creatorcontrib>Zibandeh, Noushin</creatorcontrib><creatorcontrib>Yıldırım, Selin</creatorcontrib><creatorcontrib>Trakas, Nikolaos</creatorcontrib><creatorcontrib>Zisimopoulou, Paraskevi</creatorcontrib><creatorcontrib>Küçükerden, Melike</creatorcontrib><creatorcontrib>Tașlı, Hatice</creatorcontrib><creatorcontrib>Tzartos, Socrates</creatorcontrib><creatorcontrib>Göker, Kamil</creatorcontrib><creatorcontrib>Tüzün, Erdem</creatorcontrib><creatorcontrib>Akkoç, Tunç</creatorcontrib><title>Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice</title><title>Journal of neuroinflammation</title><addtitle>J Neuroinflammation</addtitle><description>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.
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.
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.
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.</description><subject>Animals</subject><subject>Autoimmunity</subject><subject>Cells, Cultured</subject><subject>Dendritic cells</subject><subject>Dental Sac - cytology</subject><subject>Dental Sac - immunology</subject><subject>Dental Sac - transplantation</subject><subject>Female</subject><subject>Humans</subject><subject>Immunization - methods</subject><subject>Immunoglobulin G</subject><subject>Mesenchymal Stem Cell Transplantation - methods</subject><subject>Mesenchymal Stromal Cells - immunology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Muscle weakness</subject><subject>Muscle Weakness - immunology</subject><subject>Muscle Weakness - therapy</subject><subject>Myasthenia gravis</subject><subject>Receptor Protein-Tyrosine Kinases - administration & dosage</subject><subject>Receptor Protein-Tyrosine Kinases - immunology</subject><subject>Receptors, Cholinergic - administration & dosage</subject><subject>Receptors, Cholinergic - immunology</subject><subject>Stem cells</subject><subject>T cells</subject><subject>Tyrosine</subject><issn>1742-2094</issn><issn>1742-2094</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptUUtv1jAQtBCIlsIP4IIsceGS4rfjC1JVKCCKOABny3E2Xw1-lDgBtb8eR1-pWgn5sPbuzMg7g9BzSo4p7dXrSpnRoiNUdkRI2pEH6JBqwTpGjHh4536AntT6gxDOpGKP0QFTSqhe0EO0ewt5cRFPJcbgI-AEFbK_uEqtWRdI2EOM2I0p5FCX2S2hZOwSxFDaAypOa914f8D9zFArDhl_Xr9-6kJKaw7XMOIUPDxFjyYXKzy7qUfo-9m7b6cfuvMv7z-enpx3Xii1dGrsKdFCEsOBjVI45oZJSGZ8z5UhWjkuHeEj0UZPUhhjvOsHMTLSK86GgR-hN3vdy3VIMPq23eyivZxDcvOVLS7Y-5McLuyu_LZCad5L0QRe3QjM5dcKdbEp1M0Dl6Gs1TZPNSeaUNWgL_fQnYtgQ55KU_Qb3J40e40yQsmGOv4Pqp0RmjElwxRa_x6B7gl-LrXOMN3-nhK75W73uduWu91yt6RxXtxd-5bxL2j-F6lrqRs</recordid><startdate>20151209</startdate><enddate>20151209</enddate><creator>Ulusoy, Canan</creator><creator>Zibandeh, Noushin</creator><creator>Yıldırım, Selin</creator><creator>Trakas, Nikolaos</creator><creator>Zisimopoulou, Paraskevi</creator><creator>Küçükerden, Melike</creator><creator>Tașlı, Hatice</creator><creator>Tzartos, Socrates</creator><creator>Göker, Kamil</creator><creator>Tüzün, Erdem</creator><creator>Akkoç, Tunç</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20151209</creationdate><title>Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice</title><author>Ulusoy, Canan ; Zibandeh, Noushin ; Yıldırım, Selin ; Trakas, Nikolaos ; Zisimopoulou, Paraskevi ; Küçükerden, Melike ; Tașlı, Hatice ; Tzartos, Socrates ; Göker, Kamil ; Tüzün, Erdem ; Akkoç, Tunç</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c466t-6d810745093e2d54a2abf4529c8369076a35a03d0797f54999ca8b4d208632bb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Autoimmunity</topic><topic>Cells, Cultured</topic><topic>Dendritic cells</topic><topic>Dental Sac - cytology</topic><topic>Dental Sac - immunology</topic><topic>Dental Sac - transplantation</topic><topic>Female</topic><topic>Humans</topic><topic>Immunization - methods</topic><topic>Immunoglobulin G</topic><topic>Mesenchymal Stem Cell Transplantation - methods</topic><topic>Mesenchymal Stromal Cells - immunology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Muscle weakness</topic><topic>Muscle Weakness - immunology</topic><topic>Muscle Weakness - therapy</topic><topic>Myasthenia gravis</topic><topic>Receptor Protein-Tyrosine Kinases - administration & dosage</topic><topic>Receptor Protein-Tyrosine Kinases - immunology</topic><topic>Receptors, Cholinergic - administration & dosage</topic><topic>Receptors, Cholinergic - immunology</topic><topic>Stem cells</topic><topic>T cells</topic><topic>Tyrosine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ulusoy, Canan</creatorcontrib><creatorcontrib>Zibandeh, Noushin</creatorcontrib><creatorcontrib>Yıldırım, Selin</creatorcontrib><creatorcontrib>Trakas, Nikolaos</creatorcontrib><creatorcontrib>Zisimopoulou, Paraskevi</creatorcontrib><creatorcontrib>Küçükerden, Melike</creatorcontrib><creatorcontrib>Tașlı, Hatice</creatorcontrib><creatorcontrib>Tzartos, Socrates</creatorcontrib><creatorcontrib>Göker, Kamil</creatorcontrib><creatorcontrib>Tüzün, Erdem</creatorcontrib><creatorcontrib>Akkoç, Tunç</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of neuroinflammation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ulusoy, Canan</au><au>Zibandeh, Noushin</au><au>Yıldırım, Selin</au><au>Trakas, Nikolaos</au><au>Zisimopoulou, Paraskevi</au><au>Küçükerden, Melike</au><au>Tașlı, Hatice</au><au>Tzartos, Socrates</au><au>Göker, Kamil</au><au>Tüzün, Erdem</au><au>Akkoç, Tunç</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice</atitle><jtitle>Journal of neuroinflammation</jtitle><addtitle>J Neuroinflammation</addtitle><date>2015-12-09</date><risdate>2015</risdate><volume>12</volume><issue>1</issue><spage>231</spage><epage>231</epage><pages>231-231</pages><artnum>231</artnum><issn>1742-2094</issn><eissn>1742-2094</eissn><abstract>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.
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.
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.
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.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>26646841</pmid><doi>10.1186/s12974-015-0451-0</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Autoimmunity Cells, Cultured Dendritic cells Dental Sac - cytology Dental Sac - immunology Dental Sac - transplantation Female Humans Immunization - methods Immunoglobulin G Mesenchymal Stem Cell Transplantation - methods Mesenchymal Stromal Cells - immunology Mice Mice, Inbred C57BL Muscle weakness Muscle Weakness - immunology Muscle Weakness - therapy Myasthenia gravis Receptor Protein-Tyrosine Kinases - administration & dosage Receptor Protein-Tyrosine Kinases - immunology Receptors, Cholinergic - administration & dosage Receptors, Cholinergic - immunology Stem cells T cells Tyrosine |
| title | Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice |
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