title: 3D spheroid cultures improve the metabolic gene expression profiles of HepaRG cells.
abstract: 3D (three-dimensional) cultures are considered to be an effective method for toxicological studies; however, little evidence has been reported whether 3D cultures have an impact on hepatocellular physiology regarding lipid or glucose metabolism. In the present study, we conducted physiological characterization of hepatoma cell lines HepG2 and HepaRG cells cultured in 3D conditions using a hanging drop method to verify the effect of culture environment on cellular responses. Apo (Apolipoprotein)B as well as albumin secretion was augmented by 3D cultures. Expression of genes related to not only drug, but also glucose and lipid metabolism were significantly enhanced in 3D cultured HepaRG spheroids. Furthermore, mRNA levels of CYP (cytochrome P450) enzymes following exposure to corresponding inducers increased under the 3D condition. These data suggest that this simple 3D culture system without any special biomaterials can improve liver-specific characteristics including lipid metabolism. Considering that the system enables high-throughput assay, it may become a powerful tool for compound screening concerning hepatocellular responses in order to identify potential drugs.
authors.affiliation: Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan yu.takahashi@jt.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hori
authors.affiliation: Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Urashima
authors.affiliation: Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ohara
authors.affiliation: Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000418:Albumins / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods*; D065693:Cytochrome P-450 Enzyme Inducers / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells / Q000187:drug effects / Q000502:physiology; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000502:physiology*; D009853:Omeprazole / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D018874:Spheroids, Cellular; D059467:Transcriptome
chemical_list: D000418:Albumins; D001055:Apolipoproteins B; D065693:Cytochrome P-450 Enzyme Inducers; D008077:Lipoproteins, LDL; D003577:Cytochrome P-450 Enzyme System; D005947:Glucose; D009853:Omeprazole; D012293:Rifampin; D010634:Phenobarbital
keywords: 3D culture; HepG2 cells; HepaRG cells; gene expression; hanging drop