Development of a novel pathological model of inflammatory bowel disease in a dish

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18106
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Tsuruta Satoru 国立研究開発法人国立成育医療研究センター, 再生医療センター, リサーチアソシエイト (50814365)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: マクロファージ / 自然免疫 / オルガノイド / ミニ腸 / iPS細胞 / 小腸

Outline of Final Research Achievements

We finally succeeded in creating a mini-gut with internalized tissue macrophages. Tissue macrophages positively attached to the mini-gut had the same characteristics as CD14(-), IBA1(+), and CX3CR1(+) biological small intestinal tissue macrophages. Phagocytosis test of E. coli particles also confirmed that they have the ability to phagocytose pathogens. We succeeded in developing intestinal organoids with innate immune response also from the secretion of various inflammatory cytokines and chemokines. These results were accepted for publication in the Journal of the American Gastroenterological Association. This is an epoch-making bio-model that enables in vitro evaluation of the intestinal immune response, and is an achievement that will greatly contribute to the development of research on inflammatory bowel disease and drug discovery.

Free Research Field

消化器

Academic Significance and Societal Importance of the Research Achievements

腸管発生・維持・成長の過程での腸管上皮系または間葉系の細胞と腸管免疫組織との機能的連携を再現し、腸管炎症における細胞内シグナルやサイトカインシグナルを評価できるこれまでにない極めてイノベイティブな難治性腸疾患研究のバイオモデルを構築することができた。世界初の免疫組織を有する高機能腸管オルガノイドでIBDにおける腸管炎症を再現するモデルを作り出し、未だ明らかになっていない疾患原因の究明とその新たな治療開発へ展開していく。また、これが実現すればIBDのみならず腸内細菌、腸管感染症や様々な難治性腸疾患の研究へも大きく貢献するものである。