Treatment of DSS colitis with MSCs derived from MHC-homozygous iPSCs with using cynomolgus macaque
| Project/Area Number |
17K09379
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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 |
Gastroenterology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
伊藤 靖 滋賀医科大学, 医学部, 教授 (90324566)
石垣 宏仁 滋賀医科大学, 医学部, 助教 (90432301)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | DSS colitis / MSC / iPSC / cynomolgus macaque / カニクイザル / DSS腸炎 / 間葉系幹細胞 / IL-10 / BM-MSC / 移植・再生医療 / iPS細胞 |
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| Outline of Final Research Achievements |
Monkey iPS cell-derived mesenchymal stem cells (iMSCs) and monkey bone marrow-derived mesenchymal stem cells (BM-MSCs) were administered to a DSS colitis model of cynomolgus macaque, and the therapeutic effect on colitis was examined endoscopically and histologically. As a result, no therapeutic effect was observed for both iMSC and BM-MSC. Unlike human MSCs, monkey iMSCs and monkey BM-MSCs did not produce IL-10, which is one of anti-inflammatory cytokine. Therefore, iMSC-IL10 in which IL-10 was forcibly expressed in iMSCs were established and administered to treat monkey DSS colitis. Although IL-10 levels were elevated in the peripheral blood of cynomolgus monkeys treated with iMSC-IL10, no improvement in DSS colitis was observed. However, iMSC-IL10 histologically provided slight improvement of the colitis and then we ought to perform further experiments in future.
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| Academic Significance and Societal Importance of the Research Achievements |
1)下剤の投与量と投与タイミングを調整することで、カニクイザル に対し、安定した下部消化管内視鏡を行うことができた。またDSSの投与量を工夫することで、世界で初めてカニクイザルDSS腸炎モデルを作製することができた。
2)iMSC-IL10を作成し、カニクイザルに投与したところ、末梢血中でのIL-10濃度の上昇を認めたことから、iMSCを担体としたcytokine deliver systemの可能性を示すことができた。
3)iMSC-IL10を投与後に、histological scoreにおいて若干の改善を認めたことから、さらなる検討が必要と考えられた。
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Report
(4 results)
Research Products
(1 results)
