title: Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice.
abstract: 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.
authors.affiliation: Department of Neuroscience, Institute for Experimental Medical Research (DETAE), Istanbul University, Istanbul, Turkey.
authors.forename: Canan
authors.initials: C
authors.lastname: Ulusoy
authors.affiliation: Division of Pediatric Allergy and Immunology, Marmara University Faculty of Medicine, Istanbul, Turkey.
authors.forename: Noushin
authors.initials: N
authors.lastname: Zibandeh
authors.affiliation: Division of Pediatric Allergy and Immunology, Marmara University Faculty of Medicine, Istanbul, Turkey.
authors.forename: Selin
authors.initials: S
authors.lastname: Yıldırım
authors.affiliation: Department of Neurobiology, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Trakas
authors.affiliation: Department of Neurobiology, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Zisimopoulou
authors.affiliation: Department of Neuroscience, Institute for Experimental Medical Research (DETAE), Istanbul University, Istanbul, Turkey.
authors.forename: Melike
authors.initials: M
authors.lastname: Küçükerden
authors.affiliation: Department of Neuroscience, Institute for Experimental Medical Research (DETAE), Istanbul University, Istanbul, Turkey.
authors.forename: Hatice
authors.initials: H
authors.lastname: Tașlı
authors.affiliation: Department of Neurobiology, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: Socrates
authors.initials: S
authors.lastname: Tzartos
authors.affiliation: Department of Oral and Maxillofacial Surgery, Marmara University Faculty of Dentistry, Istanbul, Turkey.
authors.forename: Kamil
authors.initials: K
authors.lastname: Göker
authors.affiliation: Department of Neuroscience, Institute for Experimental Medical Research (DETAE), Istanbul University, Istanbul, Turkey. drerdem@yahoo.com.|Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Capa, Turkey. drerdem@yahoo.com.
authors.forename: Erdem
authors.initials: E
authors.lastname: Tüzün
authors.affiliation: Division of Pediatric Allergy and Immunology, Marmara University Faculty of Medicine, Istanbul, Turkey.
authors.forename: Tunç
authors.initials: T
authors.lastname: Akkoç
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003795:Dental Sac / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D005260:Female; D006801:Humans; D007114:Immunization / Q000379:methods*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018908:Muscle Weakness / Q000276:immunology / Q000628:therapy*; D020794:Receptor Protein-Tyrosine Kinases / Q000008:administration & dosage* / Q000276:immunology; D011950:Receptors, Cholinergic / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases