Crosstalks between different organs cultured in OrganS on-a-chip

2022 Fiscal Year Final Research Report

• Project Area: Science for virtual human development: Organ(s)-on-a-chips reveal systemic metabolic networks
• Project/Area Number: 20H05745
• Research Category: Grant-in-Aid for Transformative Research Areas (B)
• Allocation Type: Single-year Grants
• Review Section: Transformative Research Areas, Section (II)
• Research Institution: The University of Tokyo
• Principal Investigator: Sakai Yasuyuki 東京大学, 大学院工学系研究科(工学部), 教授 (00235128)
• Co-Investigator(Kenkyū-buntansha): 杉浦 慎治 国立研究開発法人産業技術総合研究所, 生命工学領域, 副連携研究室長 (10399496) ; 荒川 大 金沢大学, 薬学系, 准教授 (40709028)
• Project Period (FY): 2020-10-02 – 2023-03-31
• Keywords: マイクロフィジオロジカルシステム / 小腸 / 肝臓 / 腎臓 / 臓器間相互作用 / 三次元培養 / 数理モデル化

Outline of Final Research Achievements

The purpose of this project is to develop a universal multi-organ chip, observe the interactions between organs in vitro, elucidate the mechanisms, and contribute to the construction of a "virtual physiological human" that is the goal of this research area. The mechanism of the enhancement of drug metabolic activity observed in the coculture of intestine and liver cells using the organ chips was clarified. In addition, we developed high-density and highly functional liver tissues to reproduce human pharmacokinetic profiles. Furthermore, we found that the accumulation of drugs in the kidneys during hepatic bile stasis in animals is associated with decreased expression of drug efflux transporters in the kidneys, which was partially reproduced in the in vitro culture system.

Free Research Field

生物化学工学

Academic Significance and Societal Importance of the Research Achievements

複数臓器を灌流培養するチップを用いて臓器間相互作用を報告した例は，世界的にも未だ少ない．腸管と肝の薬物代謝は初回通過効果として一括りにされることが多いが，臓器チップを用いて個別臓器の寄与と両者の相互作用をも定量化できることが利点である．さらに，本研究で観測された共培養時の薬物代謝酵素の亢進について，メカニズムの一端を明らかにできたことは，今後の培養系を基礎としたヒト影響予測にとって高い価値のあるものである．