Visualization of osteoblast impairments during bone marrow GVHD

骨髓 GVHD 期间成骨细胞损伤的可视化

• 批准号: 24659216
• 负责人: MATSUSHIMA Kouji
• 金额: $ 2.5万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659216/
• 关键词: 移植・再生医療; 免疫学; 細胞・組織; 病理学; 癌

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.

本研究旨在揭示骨髓移植物抗宿主病（GVHD）过程中成骨细胞受损的细胞和分子机制。在轻度错配的小鼠GVHD模型中，ALP+成骨细胞在早期丢失，而骨髓中的骨质增生和纤维化发生在晚期。体外共培养实验表明，供体CD 4 + T细胞诱导成骨细胞系MC 3 T3和间充质干细胞C3 H10凋亡。此外，供体CD 4 + T细胞还抑制MC 3 T3的细胞周期和BMP依赖性成熟，但不抑制C3 H10。对供体CD 4 + T细胞诱导骨髓间充质细胞损伤的细胞和分子机制的进一步研究将有助于开发克服allo-HSCT后免疫缺陷的策略。

项目成果

Stress-induced production of chemokines by hair follicles regulates the trafficking of dendritic cells in skin.

• DOI: 10.1038/ni.2353
• 发表时间: 2012-06-24
• 期刊: NATURE IMMUNOLOGY
• 影响因子: 30.5
• 作者: Nagao, Keisuke;Kobayashi, Tetsuro;Moro, Kazuyo;Ohyama, Manabu;Adachi, Takeya;Kitashima, Daniela Y.;Ueha, Satoshi;Horiuchi, Keisuke;Tanizaki, Hideaki;Kabashima, Kenji;Kubo, Akiharu;Cho, Young-hun;Clausen, Bjorn E.;Matsushima, Kouji;Suematsu, Makoto;Furtado, Glaucia C.;Lira, Sergio A.;Farber, Joshua M.;Udey, Mark C.;Amagai, Masayuki
• 通讯作者: Amagai, Masayuki

Delayed and aberrant immunological reconstitution in allogeninc hematopoietic stem cell transplantation

异基因造血干细胞移植中的延迟和异常免疫重建

• 发表时间: 2013
• 作者: Hashimoto S;Ogoshi K;Sasaki A;Abe J;Qu W;Nakatani Y;Ahsan B;Oshima K;Shand FH;Ametani A;Suzuki Y;Kaneko S;Wada T;Hattori M;Sugano S,Morishita S;Matsushima K;Keisuke Nagao;Kouji Matsushima
• 通讯作者: Kouji Matsushima

骨髄GVHDにおける間葉系細胞障害の細胞・分子機序

骨髓GVHD间充质细胞损伤的细胞和分子机制

• 发表时间: 2013
• 作者: 上羽悟史;小杉瑞葉;王泳;横山顕大;朝比奈晏那;松島綱治
• 通讯作者: 松島綱治

Destruction of hematopoietic niche after allogenic hematopoietic stem cell transplantation

异基因造血干细胞移植后造血生态位的破坏

• 发表时间: 2012
• 作者: 上羽悟史;小杉瑞葉;王泳;横山顕大;朝比奈晏那;松島綱治;Kouji Matsushima;小杉 瑞葉;小杉 瑞葉
• 通讯作者: 小杉 瑞葉

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