Differentiation of human iPS cells into hepatocytes and enterocytes: Development of first pass effect assessment model

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293036
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Nagoya City University
• Principal Investigator: Matsunaga Tamihide 名古屋市立大学, 薬学研究科(研究院), 教授 (40209581)
• Co-Investigator(Kenkyū-buntansha): 大森 栄 信州大学, 医学部附属病院, 教授 (70169069) ; 永田 清 東北医科薬科大学, 薬学部, 教授 (80189133)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ヒトiPS細胞 / 分化誘導 / 肝細胞 / 腸管上皮細胞 / 初回通過効果 / 薬物代謝酵素 / 薬物トランスポーター

Outline of Final Research Achievements

Human induced pluripotent stem (iPS) cells are expected to be applicable not only in regenerative medicine but also in drug development such as pharmacokinetic and toxicokinetic studies. In this study, the differentiation in 3D sphere culture was increased the gene expressions or the activity of drug metabolizing enzymes and improved the function of human iPS cell-derived hepatocytes.　The small-molecule compounds, PD98059, 5-aza-2-deoxycytidine and A-83-01, were effective in generating pharmacokinetically functional enterocytes from human iPS cells. MEK, DNMT, and TGF-β inhibitors can be used to promote the differentiation of human iPS cells into pharmacokinetically functional enterocytes.

Free Research Field

幹細胞生物学