3D spheroid cultures improve the metabolic gene expression profiles of HepaRG cells

  • Yu Takahashi
    Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan
  • Yuji Hori
    Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan
  • Tomohisa Yamamoto
    Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan
  • Toshiki Urashima
    Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan
  • Yasunori Ohara
    Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan
  • Hideo Tanaka
    Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan

抄録

<jats:p>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.</jats:p>

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