2013 Fiscal Year Final Research Report
Visualization of osteoblast impairments during bone marrow GVHD
Project/Area Number |
24659216
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Single-year Grants |
Research Field |
Immunology
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Research Institution | The University of Tokyo |
Principal Investigator |
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Project Period (FY) |
2012-04-01 – 2014-03-31
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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.
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