Development of functional hepatocytes from human liver organoids for pharmaceutical research

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20717
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Osaka University
• Principal Investigator: Ueyama Yukiko (鳥羽由希子) 大阪大学, 大学院薬学研究科, 助教 (10904930)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 肝細胞 / オルガノイド / 薬物代謝酵素

Outline of Final Research Achievements

Human liver organoids are expected to be the new hepatocyte source used for preclinical in vitro studies of drug metabolism and disposition. Although they showed long-term proliferation, their hepatic functions were low. Therefore, it is necessary to enhance hepatic functions of human liver organoids. Here, we propose a novel method for 2D-cultured hepatic differentiation from human liver organoids.The gene expression level of albumin in human liver organoids-derived hepatocytes (Org-HEPs) increased to about 875-fold of human liver organoids. Metabolic activities of major Cytochrome P450 (CYP) enzymes were examined. The metabolic activities of CYP1A2, CYP2C8, CYP2E1 and CYP3A4 were at a level comparable to that of PHHs-48hr. These results suggested that human liver organoids could be differentiated into highly functional hepatocytes in 2D culture. In this study, we succeeded in developing the differentiation method from human liver organoids into functional hepatocytes.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

一般的なオルガノイド培養状態では、種々の被検化合物が細胞外マトリクスに捕捉されることが懸念され、創薬研究への利用には不向きであった。そこで、汎用性の高い肝細胞を肝臓オルガノイドから得るために、二次元培養にて分化・成熟化を試みた。その結果、二次元培養にてヒト肝細胞と同等の高い機能を持った肝細胞の作製に成功した。本研究で開発した肝細胞は、創薬研究への応用が実現可能であり、医薬品開発の加速化に大きく貢献すると考えられる。