| Project/Area Number |
16H05490
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatric surgery
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| Research Institution | Keio University |
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Principal Investigator |
Ken Hoshino 慶應義塾大学, 医学部(信濃町), 特任准教授 (70190197)
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| Co-Investigator(Kenkyū-buntansha) |
山田 洋平 慶應義塾大学, 医学部(信濃町), 特任助教 (60383816)
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| Research Collaborator |
KISU Iori
ISHIGAKI Hirohito
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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 |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | 小腸移植 / 拒絶反応 / 免疫抑制剤 / カニクイザル / Madcam-1 / リンパ球ホーミング / キメリズム / 腸管リンパ球 / 腸管免疫 |
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| Outline of Final Research Achievements |
In this study, nonhuman primate-model of small bowel transplantation has been established and immunological monitoring for CD4 helper T cells in peripheral blood and immunohistochemistry for α4β7integrin positive T lymphocytes in the allografts were performed. Average rejection-free survival of small bowel grafts with conventional immunosuppression (consisting of Tacrolimus and steroids) was 23.3 days. Increased anti-donor response was observed in mixed lymphocyte reaction tests, which were measured by ELISPOT assay. In addition, the duration and the extent of peripheral chimerism, which was measured by the percentage of donor lymphocytes among total lymphocytes, was correlated with the rejection-free survival days after transplantation.
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| Academic Significance and Societal Importance of the Research Achievements |
小腸移植は2018年に保険承認され、腸管不全に対する根治的治療である小腸移植が普及すると考えられる。小腸移植の最大の障壁はその中長期予後であり、予後改善のための新規免疫抑制剤の効果を検証する必要がある。カニクイザルを使用した臓器移植モデルは多く報告されているが、小腸移植モデルの報告はほとんどなく、本研究にて確立された異所性小腸移植モデルによって、臨床応用可能な免疫抑制剤の効果をin vivoで評価可能となった。新規免疫抑制剤と従来の免疫抑制剤の指摘な組み合わせの考案や拒絶反応早期発見研究のプラットフォーム、さらにはヒト臨床に近似した腸管でのアロ免疫応答の解明に寄与することが期待される。
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