title: Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis.
abstract: Multiple sclerosis (MS) is a major neuroinflammatory demyelinating disease of the CNS. Current MS treatments, including immunomodulators and immunosuppressants, do not result in complete remission. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells derived from dental pulp. Both SHED and SHED-conditioned medium (SHED-CM) exhibit immunomodulatory and regenerative activities and have the potential to treat various diseases. In this study, we investigated the efficacy of SHED-CM in treating experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. EAE mice treated with a single injection of SHED-CM exhibited significantly improved disease scores, reduced demyelination and axonal injury, and reduced inflammatory cell infiltration and proinflammatory cytokine expression in the spinal cord, which was associated with a shift in the microglia/macrophage phenotype from M1 to M2. SHED-CM also inhibited the proliferation of myelin oligodendrocyte glycoprotein-specific CD4(+) T cells, as well as their production of proinflammatory cytokines in vitro. Treatment of EAE mice with the secreted ectodomain of sialic acid-binding Ig-like lectin-9, a major component of SHED-CM, recapitulated the effects of SHED-CM treatment. Our data suggest that SHED-CM and secreted ectodomain of sialic acid-binding Ig-like lectin-9 may be novel therapeutic treatments for autoimmune diseases, such as MS.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan;
authors.forename: Chiaki
authors.initials: C
authors.lastname: Shimojima
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan; and Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama 236-0004, Japan akihito@med.nagoya-u.ac.jp htake@yokohama-cu.ac.jp.
authors.forename: Hideyuki
authors.identifier: 0000-0001-5912-7581
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan; and.
authors.forename: Shijie
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan; and.
authors.forename: Bijay
authors.identifier: 0000-0003-3813-113X
authors.initials: B
authors.lastname: Parajuli
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan;
authors.forename: Hisashi
authors.identifier: 0000-0001-9181-8948
authors.initials: H
authors.lastname: Hattori
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan; and.
authors.forename: Akio
authors.initials: A
authors.lastname: Suzumura
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan;
authors.forename: Hideharu
authors.identifier: 0000-0003-0248-7476
authors.initials: H
authors.lastname: Hibi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan;
authors.forename: Minoru
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan; akihito@med.nagoya-u.ac.jp htake@yokohama-cu.ac.jp.
authors.forename: Akihito
authors.identifier: 0000-0002-9206-1243
authors.initials: A
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology*; D009103:Multiple Sclerosis / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000378:metabolism; D014094:Tooth, Deciduous / Q000502:physiology / Q000601:surgery
chemical_list: D015703:Antigens, CD; D017077:Culture Media, Conditioned; D016207:Cytokines; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C445081:myelin oligodendrocyte glycoprotein (35-55); C000611707:siglec-9 protein, mouse