| Project/Area Number |
16K10427
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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 | Department of Clinical Research, National Hospital Organization Kure Medical Center (2017-2018)
Hiroshima University (2016) |
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Principal Investigator |
Ishiyama Kohei 独立行政法人国立病院機構(呉医療センター臨床研究部), その他部局等, その他 (50437589)
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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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 膵島移植 / 1型糖尿病 / NK細胞 / 間葉系幹細胞 / プロスタグランジン / 免疫学 / 移植 / 糖尿病 |
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| Outline of Final Research Achievements |
Using the mouse intraportal islet transplantation model, we have reported that the cytotoxic activity of intrahepatic NK cells on the transplanted islets is enhanced after islet transplantation and it caused the islet graft destruction. We confirmed that activation of intrahepatic NK cells in the IBMIR environment, which involved in acute islet injury after islet transplantation, disturbed transplanted islet engraftment.
In order to control intrahepatic immune activity, mesenchymal stem cells (MSCs), having a cytotoxic activity inhibitory effect by various soluble factors such as PGE2, are activated with inflammatory cytokines and then cotransplanted with islet transplantation. We demonstrated that the ability to produce PGE2 was well enhanced to regurate the intrahepatic NK cells activation after islet transplantation. Furthermore, we demonstrated that co-administration of activated MSCs contributes to a remarkable improvement effect on islet graft survival.
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| Academic Significance and Societal Importance of the Research Achievements |
本邦において膵島移植が普及するには移植効率の向上が必須であり、初回膵島移植後の肝臓内免疫細胞活性化メカニズムと、免疫感作に伴う再移植後の膵島傷害メカニズムを解明し、肝臓内免疫細胞活性を制御する治療戦略を確立することは有用と考えられる。
本研究で、十分量の膵島と複数回の移植でのみ治療効果が認められていた膵島移植が、活性化間葉系幹細胞を同時投与することで、少量でも効果が期待できる可能性があることを証明した。
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