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2013 Fiscal Year Final Research Report

Visualization of osteoblast impairments during bone marrow GVHD

Research Project

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Project/Area Number 24659216
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionThe University of Tokyo

Principal Investigator

MATSUSHIMA Kouji  東京大学, 大学院医学系研究科, 教授 (50222427)

Project Period (FY) 2012-04-01 – 2014-03-31
Keywords移植・再生医療 / 免疫学 / 細胞・組織 / 病理学 / 癌
Research Abstract

We aimed to reveal the cellular and molecular mechanisms of the osteoblast impairments during bone marrow GVHD. In a minor mismatched mouse GVHD model, ALP+ osteoblasts were lost in the early phase, whereas hyperostosis and fibrosis in the marrow occured in late phase. Ex vivo co-culture experiments demonstrated that donor CD4+ T cells induced apoptosis in osteoblastic cell line MC3T3 and mesenchymal stem cell C3H10. In addition, donor CD4+ T cells also suppressed cell cycle and BMP dependent maturation of MC3T3 but not C3H10. Further studies on the cellular and molecular mechanisms of donor CD4+ T cell-induced impairments in bone marrow mesenchymal cells would lead to the development of strategies to overcome immuno-deficiency after allo-HSCT.

  • Research Products

    (7 results)

All 2014 2013 2012

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (4 results)

  • [Journal Article] Bone marrow graft-versus -host disease : evaluation of its clinical impact on disrupted hematopoiesis after allogeneic hematopoietic stem cell transplantation2014

    • Author(s)
      Shono Y, Ueha S, Matsushima K, 他
    • Journal Title

      Biol Blood Marrow Transplant

      Volume: 4 Pages: 495-500

    • DOI

      10.1016/j.bbmt.2013.12.568

    • Peer Reviewed
  • [Journal Article] Coordinated Changes in DNA Methylation in Antigen-Specific Memory CD4 T Cells2013

    • Author(s)
      Hashimoto S, Matsushima K, 他
    • Journal Title

      J Immunol

      Volume: 190 Pages: 4076-4091

    • DOI

      10.4049/jimmunol.1202267

    • Peer Reviewed
  • [Journal Article] Stress-induced production of chemokines by hair follicles regulates the trafficking of dendritic cells in skin2012

    • Author(s)
      Nagao K, Ueha S, Matsushima K, 他
    • Journal Title

      Nat Immunol

      Volume: 13 Pages: 744-752

    • DOI

      10.1038/ni.2353

    • Peer Reviewed
  • [Presentation] Delayed and aberrant immunological reconstitution in allogeninc hematopoietic stem cell transplantation2013

    • Author(s)
      Kouji Matsushima
    • Organizer
      11th World Congress on Inflammation
    • Place of Presentation
      Natal(Brazil)
    • Year and Date
      2013-09-21
  • [Presentation] 骨髄GVHDにおける間葉系細胞障害の細胞・分子機序2013

    • Author(s)
      上羽 悟史
    • Organizer
      第34回日本炎症・再生医学会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2013-07-02
  • [Presentation] Bone marrow dysfunction and defective B lymphopoiesis during chronic GVHD2012

    • Author(s)
      小杉 瑞葉
    • Organizer
      第41回日本免疫学会
    • Place of Presentation
      神戸国際展示場(兵庫)
    • Year and Date
      2012-12-05
  • [Presentation] Destruction of hematopoietic niche after allogenic hematopoietic stem cell transplantation2012

    • Author(s)
      小杉 瑞葉
    • Organizer
      第34回日本炎症再生医学会
    • Place of Presentation
      ホテル日航福岡(福岡)
    • Year and Date
      2012-07-05

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Published: 2015-06-25  

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