title: 3D spheroid culture of hESC/hiPSC-derived hepatocyte-like cells for drug toxicity testing.
abstract: Although it is expected that hepatocyte-like cells differentiated from human embryonic stem (ES) cells or induced pluripotent stem (iPS) cells will be utilized in drug toxicity testing, the actual applicability of hepatocyte-like cells in this context has not been well examined so far. To generate mature hepatocyte-like cells that would be applicable for drug toxicity testing, we established a hepatocyte differentiation method that employs not only stage-specific transient overexpression of hepatocyte-related transcription factors but also a three-dimensional spheroid culture system using a Nanopillar Plate. We succeeded in establishing protocol that could generate more matured hepatocyte-like cells than our previous protocol. In addition, our hepatocyte-like cells could sensitively predict drug-induced hepatotoxicity, including reactive metabolite-mediated toxicity. In conclusion, our hepatocyte-like cells differentiated from human ES cells or iPS cells have potential to be applied in drug toxicity testing.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takayama
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawabata
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Nagamoto
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kishimoto
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Tashiro
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sakurai
authors.forename: Masashi
authors.initials: M
authors.lastname: Tachibana
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Kanda
authors.forename: Takao
authors.initials: T
authors.lastname: Hayakawa
authors.forename: Miho Kusuda
authors.initials: MK
authors.lastname: Furue
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D039904:Pluripotent Stem Cells / Q000166:cytology*; D018675:Toxicity Tests / Q000379:methods*