| Project/Area Number |
18K07995
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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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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Yamada Atsuo 東京大学, 医学部附属病院, 助教 (80534932)
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| Co-Investigator(Kenkyū-buntansha) |
平田 喜裕 東京大学, 医科学研究所, 准教授 (10529192)
新倉 量太 東京大学, 医学部附属病院, 助教 (90625609)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 小腸 / 潰瘍 / 上皮細胞 / 分化障害 / オルガノイド / 炎症 / 出血 / 小腸潰瘍 / 上皮機能異常 |
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| Outline of Final Research Achievements |
To investigate the molecular pathogenesis of small intestinal ulcers, we used organoid culture model of human and murine small intestine. Human small intestinal disease specimens obtained using double-balloon endoscopy were cultured in Matrigel with organoid culture media. In contrast to other small intestinal disease epithelium such as cancer, epithelium from small intestinal ulcers did not grow in organoid culture, suggesting the impairment of epithelial differentiation. Using mouse small intestinal organoid and dendritic cell co-culture model, we found organoid differentiation is perturbed by dendritic cells, and acetylcholine analogue sufficiently ameliorated this phenotype. Knockout mouse of a7nAchR showed the critical role of acetylcholine in the control of intestinal epithelial differentiation in murine colitis model.
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| Academic Significance and Societal Importance of the Research Achievements |
小腸疾患は診断技術の発達により以前ほど希少疾患ではなくなっているものの、他部位の疾患にくらべて培養細胞モデルなどの基礎研究リソースが限られていた。オルガノイド培養技術の開発は非腫瘍性疾患や正常上皮の研究に革新的な発展をもたらしている。本研究では小腸潰瘍性疾患の上皮の分化障害と特殊性を明らかにし、マウス小腸オルガノイドを用いた治療戦略を開発することができ、今後の小腸潰瘍性疾患研究の基盤となる知見が得られた。
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