| Project/Area Number |
16K10416
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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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| Research Field |
General surgery
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| Research Institution | Hokkaido University |
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Principal Investigator |
Goto Ryoichi 北海道大学, 医学研究院, 特任助教 (10645287)
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| Co-Investigator(Kenkyū-buntansha) |
山下 健一郎 北海道大学, 医学研究院, 特任教授 (00399940)
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| Research Collaborator |
Fukasaku Yasutomo
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | ヒト化マウス / 抗HLA抗体 / 移植 / HLA抗体 / NSGマウス / 皮膚移植モデル / 血管移植 / 慢性拒絶反応 / 肝移植 / 免疫抑制細胞 |
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| Outline of Final Research Achievements |
In this study our aim is to clarify the role of anti-donor HLA antibody (DSA) and find its effective treatment in organ transplantation. To establish the humanized mouse model, we obtained a human vessel or skin from the patient who underwent a colectomy or skin transplantation and transplanted them to severe immunodeficient mice. However, we could not overcome an arterial thrombosis and tissue injuries after transplantation due to innate immune responses in immunodeficient mice. Therefore, we decided to change the immunodeficient mice to another one. Also, we collected the serum samples including DSAs from the liver transplant recipients. We identified the correlation between the mean fluorescence intensities (MFI) of the DSA and graft fibrosis in the recipients who had been transplanted the liver graft from elderly donors. Thus, we identified the clinical impact of DSA in liver transplantation, however, the underlying mechanism warrant further study by using humanized mouse model.
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| Academic Significance and Societal Importance of the Research Achievements |
臨床検体を用いたヒト化マウスモデルの可能性を探索し、免疫不全マウスの種類によって自然免疫の関与により作成が困難であったが、この知見はヒト化マウスの学術的意義として重要であった。一方、大腸癌患者の腸管膜動脈やヒト皮膚移植片の余剰組織を用いるヒト化マウス研究は、高次動物や臨床でないと検討しえないヒト化抗体やヒト細胞治療などの臨床前研究として有用なツールとなる。特にマウスのMHC-class II抗原の発現はヒトと異なり、抗体研究でのヒト化マウス移植モデルは貴重である。本研究で明らかになった抗ドナーHLA抗体の臨床的意義は、臨床にリアルタイムで反映しえる重要な知見である。
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