| Project/Area Number |
18K08597
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 抗体関連型拒絶反応 / ヒト化マウス / 慢性拒絶反応 / 臓器移植 / 拒絶反応 |
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| Outline of Final Research Achievements |
The purpose of this study is to elucidate the antibody-related rejection mechanism of human immunocompetent cells, which was difficult to analyze in the past, by using a humanized mouse model. When recipient and donor peripheral blood mononuclear cells were mixed and cultured in vitro on mouse fibroblasts expressing a high expression of human CD40 ligand that induces a HLA antibody production promoting signal and administered to NSG mice, a sufficient amount of HLA antibody production was produced. It has become possible to produce HLA antibody-producing humanized mice that can be obtained at a high rate. In addition, a humanized mouse model was constructed in which only donor-specific HLA antibodies were suppressed, and similarly sufficient HLA antibody production was observed for human BAFF-BAFF receptor signal addition and recipient regulatory T cell depletion.
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| Academic Significance and Societal Importance of the Research Achievements |
臓器移植という医療は免疫抑制剤や治療法の進歩により術後早期の生存率/生着率が近年向上したが、長期生着例において慢性拒絶反応による移植片機能不全は長期成績が向上しない原因として位置づけされている。しかし慢性抗体関連型拒絶反応の原因や治療法は未だ解明されていない。従来解析困難であったヒト免疫担当細胞の抗体関連型拒絶反応メカニズムをヒト化マウスモデルにより解明し、慢性拒絶反応に対する個別化治療への臨床応用は大きな学術的意義をもたらすことが期待できる。本研究成果によって同種移植における慢性拒絶反応克服の可能性や抗ドナーHLA抗体陽性レシピエントに対する移植適応の拡大が大いに期待できる。
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