Development and clinical evaluation of hepatitis onset model of chimeric mice with iPS-derived human hepatocytes

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293176
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nagoya City University
• Principal Investigator: Tanaka Yasuhito 名古屋市立大学, 医学(系)研究科(研究院), 教授 (90336694)
• Co-Investigator(Kenkyū-buntansha): MATSUNAGA Tamihide 名古屋市立大学, 大学院薬学研究科, 教授 (40209581)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 肝炎ウイルス / HBV / iPS細胞 / キメラマウス

Outline of Final Research Achievements

In the differentiation to hepatocytes from human iPS cells, it was revealed that the HDAC inhibitor valproic acid in combination with cytokines induce differentiation cells into hepatic progenitor cells followed by maturation into functional hepatocytes. The hepatocytes formed a spheroid by the three-dimensional culture, and the gene expression of CYP3A which is hepatocytes marker and drug metabolizing enzyme is markedly higher than that in 2D cultures. The 3D-cultured iPS-hepatocyte spheroids were transplanted into the portal vein of highly immunodeficient NOG mice (TK-NOG) that is induced liver injury by ganciclovir treatment. At one week post-injection of hepatic spheroids, human albumin levels elevated temporarily.

Free Research Field

肝臓病学