| Project/Area Number |
18K16306
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 免疫寛容 / 骨髄由来免疫抑制細胞 / 移植医療 / 肝移植 / 外科 / ラット / 骨髄由来免疫抑制剤棒 |
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| Outline of Final Research Achievements |
In the present study, we investigated the immunosuppressive mechanism of myeloid-derived suppressor cells (MDSCs) by comparing rejection groups and immunotolerance groups in the rat liver transplantation model and examined the effect of cell therapy using MDSCs. First, the median survival time of this model was 10 days, but the survival time of 100 days or more was obtained by the administration of tacrolimus, which was considered to be an ideal tolerance model. Next, it was shown that MDSCs were induced in blood, spleen, and bone marrow in tolerance groups, and also in the graft liver. In addition, the cell therapy of MDSCs separated by magnetic cell separation extended the survival time of recipients in this model.
This study shows that MDSCs contribute to immunosuppression in liver transplantation and that the cell therapy reduced rejection.
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| Academic Significance and Societal Importance of the Research Achievements |
移植医療において移植臓器に対する宿主の拒絶反応は重要な問題である。免疫抑制剤を使用せずとも拒絶反応を起こすことなく、移植臓器が生着する免疫寛容は理想的な状態であるが拒絶反応の制御は免疫抑制剤に頼っているのが現状である。本研究ではラット肝移植モデルを用いて免疫寛容群において骨髄由来免疫抑制細胞（MDSCs）が誘導されていること、MDSCｓを用いた細胞療法によって拒絶反応を抑制することが示された。今後免疫寛容誘導のメカニズムの解明ならびに免疫誘導療法の開発によって免疫抑制剤服用に伴う問題が回避され、また医療費の軽減につながるものと考えられる。
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