Establishment of novel research platform for food and nutrition science using physiologically-relevant human intestinal organoids

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K05928
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38050:Food sciences-related
• Research Institution: The University of Tokyo
• Principal Investigator: Takahashi Yu 東京大学, 大学院農学生命科学研究科(農学部), 助教 (30835377)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: iPS細胞 / 小腸オルガノイド / Caco-2細胞 / レンチウイルス / CYP誘導 / スクリーニング

Outline of Final Research Achievements

Organoids are self-organizing cell clumps composed of tissue-specific stem cells and their differentiated cells in three-dimensional cultures. They are recognized as physiologically relevant in vitro models that recapitulate in vivo functions and structures of specific organs, and we worked on the development of methods to use them. We established mouse L cells stably expressing the cytokines Wnt3a, R-spondin1, Noggin, and HGF by lentiviral infection. Using conditioned medium from the cells as culture medium, we were able to continuously culture human intestinal organoids at a lower cost than using commercially available recombinant proteins. Furthermore, we found that CYP3A4 induction, SGLT1-mediated glucose transport, and MTP-dependent chylomicron secretion occurred in organoid-derived monolayer intestinal epithelial cells, but not in Caco-2 cells. Taken together, we established a platform to routinely use human intestinal organoids with highly physiological functions.

Free Research Field

食品科学

Academic Significance and Societal Importance of the Research Achievements

小腸オルガノイドの利用には，手間に加え膨大なコストを要する。本研究では、培養コストを従来よりも1/100に低減させ，さらに実験者誤差が生じにくい操作方法の確立に成功した。また，小腸オルガノイドでは様々な代謝機能が従来の細胞に比べて高いことを具体的に示した。以上の結果は，特に基礎研究におけるオルガノイドの活用を促進し，これまでに見出せていないヒトバイオロジーの解明に大きく貢献することが期待される。