Construction of high-throughput drug discovery screening system using bile duct organoids and fluid devices

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19490
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Tokai University
• Principal Investigator: KAMIYA Akihide 東海大学, 医学部, 准教授 (30321904)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: ヒト多能性幹細胞 / 多発肝のう胞 / 流体デバイス

Outline of Final Research Achievements

In this study, we established a method to culture human iPS cell-derived liver tissue using self-aggregation ability, and the genome editing method to construct a human iPS cell-derived liver tissue system that mimics polycystic liver diseases. In addition to searching for transcriptional regulatory factors related to the maturation of liver progenitor cells, we constructed an aggregation culture system using a fluidic device. We found that Klf15 and other transcription factors were important for in vitro maturation of hepatic progenitor cells. Based on these findings, we are working to establish a culture system to analyze the correlation between genetic mutations that control hepatic cysts and pathological conditions.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

多発肝のう胞は難治性の希少疾患であり、根治療法としては肝移植があげられる。しかし、ドナー不足などの問題点も多い。またヒトとマウスの変異遺伝子の機能の種差の違いから、実験動物を用いた病態モデルの構築も進んでいない。本研究で示したヒト多能性幹細胞とゲノム編集技術を用いたin vitro肝のう胞病態解析モデルは、今後の新規原因遺伝子の探索を含めて病気治療の新たな開発に向けた貢献が期待できる。