| Project/Area Number |
18K15696
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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 52050:Embryonic medicine and pediatrics-related
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| Research Institution | National Center for Child Health and Development |
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Principal Investigator |
Machida Masakazu 国立研究開発法人国立成育医療研究センター, 細胞医療研究部, (非)研究員 (50450622)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 小腸オルガノイド / バイオモデル / 炎症性腸疾患 / 再生医学 / オルガノイド / 小腸 / iPS細胞 |
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| Outline of Final Research Achievements |
We have developed three-dimensional tissues (mini-guts) that have peristaltic movement, absorption and secretion functions of human intestine in a petri dish. In this study, we applied this unique mini-gut technology to develop a bioresource that can simultaneously visualize and observe intestinal stem cells (LGR5) and intestinal plexus maturation (PHOX2B) over time as a system that can visualize human intestinal development. In the differentiation process of the mini guts, the double positive dynamic phase of LGR5 positive (green fluorescence) and PHOX2B (red fluorescence) was able to be confirmed. In addition, we succeeded in producing a mini-gut, in which monocytes are produced from pluripotent stem cells and macrophages are formed in the organoid to exert tissue macrophage function. The result which contributed to the progress of the intractable enterocolitis research was obtained.
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| Academic Significance and Societal Importance of the Research Achievements |
炎症性腸疾患（inflammatory bowel diseases：IBD）の患者数は年々増え厚生労働省難治性疾患の中で患者数が最も多い。特に近年問題になっているのが、6歳未満で発症する重篤な炎症性腸疾患（VEO-IBD）である。複雑な病態を解明し、診断や新たな治療薬の開発を可能にする基礎研究の大きな進展が強く望まれている。in vitroで腸の発生が再現でき生体の小腸がもつ複雑な機能を合わせもったミニ腸モデルを開発し、発生の理解とともに行う疾患研究と、さらにVEO-IBDの診断・治療開発へと展開できる研究を今行う必要がある。本研究の成果は、成育期難治性腸疾患研究の発展に貢献する成果である。
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