Establishment of hepatobiliary connection ex vivo

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K05843
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38030:Applied biochemistry-related
• Research Institution: The University of Tokyo (2021-2022); Sapporo Medical University (2020)
• Principal Investigator: Tanimizu Naoki 東京大学, 医科学研究所, 准教授 (00333386)
• Co-Investigator(Kenkyū-buntansha): 三高 俊広 札幌医科大学, 医学部, 教授 (50231618)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 上皮組織

Outline of Final Research Achievements

Inside the liver, hepatocytes and biliary epithelial cells (BECs) form bile canaliculi and bile ducts, respectively, which are interconnected to establish the bile excretion system for transporting the bile produced by hepatocytes into the duodenum. We applied an organoid culture technique on hepatocyte progenitors and BECs, we established a novel hepato-biliary tubular organoid (HBTO) in which bile acid and bilirubin up-taken by hepatocytes are secreted into bile ducts within the organoid.
We targeted two types of liver injury, steatosis and cholestasis, to generate hepatic injury models with HBTO. By incubating HBTOs with free fatty acids, lipid droplets were accumulated inside hepatocytes. When troglitazone that inhibits bile salt export pump (BSEP) was added to culture medium, bile acids were accumulated in hepatocytes instead of secreted into bile canaliculi and bile ducts.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

我々は肝臓の上皮組織である肝細胞の毛細胆管と胆管の接続をin vitroで再現することに初めて成功した。臓器再生において、隣接する組織の空間配置を制御することは非常に重要であり、上皮組織形成の理解および応用のいずれの面からも本研究成果は学術的・社会的意義が高いものである。