Polarity formation of human iPS cell-derived hepatocytes and development of a system to evaluate drug-induced liver injury

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08341
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tokai University
• Principal Investigator: Tsuruya Kota 東海大学, 医学部, 講師 (00725377)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 薬物性肝障害 / iPS細胞

Outline of Final Research Achievements

Drug-induced liver injury (DILI) is a condition that can be induced by various drugs, leading to liver failure and hindering the treatment of underlying diseases. In this study, we induced high-functioning hepatocytes with appropriate cellular polarity from human induced pluripotent stem (iPS) cells and developed a system for hepatotoxicity assessment. We identified KLF15 as a factor capable of inducing liver function and cellular polarity. Forced expression of KLF15 significantly increased the expression of liver metabolic enzymes (TAT, CPS1, CYP). Additionally, differentiation induction in 3D culture using extracellular matrix significantly increased the expression of drug transporters (MRP3, OATP1A2, OATP1B1, OATP1B3). This iPS cell-based technology contributes to the development of a system capable of predicting DILI.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究は、薬物性肝障害の予測と評価のための技術基盤を目的とする。高機能な肝細胞をヒトiPS細胞から誘導し、肝毒性評価システムを構築することで、医薬品開発の初期段階でのDILIリスクをより正確に予測可能となる。本研究では、ヒトiPS細胞へのKLF15の強制発現により、肝細胞の機能的成熟を促進する新たなアプローチを示した。この技術は、医薬品開発や再生医療や肝疾患の治療にも応用可能であると考えられる。