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Demyelinating Disorders

開催日 2014/9/11
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Stem cells from human exfoliated deciduous teeth-conditioned media ameliorate experimental autoimmune encephalomyelitis

  • P1-329
  • 下島 千明 / Chiaki Shimojima:1 山本 朗仁 / Akihito Yamamoto:1 金 世杰 / Shijie Jin:3 竹内 英之 / Hideyuki Takeuchi:2 服部 宇 / Hisashi Hattori:1 錫村 明生 / Akio Suzumura:2 上田 実 / Minoru Ueda:1 
  • 1:名古屋大院・医・顎顔面外科学 / Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine 2:名古屋大環境医・神経免疫学 / Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University 3:名古屋大環境医・病態神経科学 / Department of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University 

Background : Multiple sclerosis (MS) is a major neuroinflammatory demyelinating disease of the central nervous system (CNS). The current treatments for MS by immunomodulators and immunosuppressants have not achieved complete remission yet. Stem cells from human exfoliated deciduous teeth (SHED) are mesenchymal stem cells that have a therapeutic potential for various diseases. As well as SHED, SHED-conditioned media (SHED-CM) also exert immunosuppressive and regenerative activities. In this study, we investigated the efficacy of SHED-CM in experimental autoimmune encephalomyelitis (EAE) as mouse models of MS.

Methods : Protocols for animal experiments were approved by the Animal Experiment Committee of Nagoya University. EAE was induced in 8 week old female C57BL/6J mice by subcutaneous immunization with 200 μl of 200 μg MOG35-55 peptide with complete Freund's adjuvant. 200 ng pertussis toxin was injected intraperitoneally at the post-immunized day 0 and 2. Mice received a single intravenous injecion of 500 μl SHED-CM or DMEM from the tail vein at the disease peak (the post-immunized day 14). Mice were assessed daily according to EAE clinical score. Mice were sacrificed for histologic and biochemical assessments at the post-immunized day 16 or 28. As the ex vivo study, splenic CD4+ Th cells were cultured in SHED-CM or DMEM for 72 h. Cell proliferation and cytokine production were examined using specific ELISAs.

Results : Single injection of SHED-CM significantly improved EAE, associated with the reduction in the extent of demyelination and inflammatory cell infiltration in the spinal cord. Treatment with SHED-CM reduced the expression levels of such pro-inflammatory cytokines as IL-2, IFN-γ and IL-17 in the spinal cord and splenic CD4+ Th cells.

Conclusion : SHED-CM exhibited remarkable immunosuppressive and neuroprotective properties. SHED-CM may provide a novel therapeutic strategy toward MS.

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