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Culture of HepG2 liver cells on three dimensional polystyrene scaffolds enhances cell structure and function during toxicological challenge

Periodical: J Anat ISBN: 0021-8782 (Print)  Number: 4  Date: 2007/08/23  Language: eng  Pages: 567-76

Authors:Bokhari, M., Carnachan, R. J., Cameron, N. R., Przyborski, S. A.
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Abstract
Cultured cells are dramatically affected by the micro-environment in which they are grown. In this study, we have investigated whether HepG2 liver cells grown in three dimensional (3-D) cultures cope more effectively with the known cytotoxic agent, methotrexate, than their counterparts grown on traditional two dimensional (2-D) flat plastic surfaces. To enable 3-D growth of HepG2 cells in vitro, we cultured cells on 3-D porous polystyrene scaffolds previously developed in our laboratories. HepG2 cells grown in 3-D displayed excellent morphological characteristics and formed numerous bile canaliculi that were seldom seen in cultures grown on 2-D surfaces. The function of liver cells grown on 3-D supports was significantly enhanced compared to activity of cells grown on 2-D standard plasticware. Unlike their 2-D counterparts, 3-D cultures were less susceptible to lower concentrations of methotrexate. Cells grown in 3-D maintained their structural integrity, possessed greater viability, were less susceptible to cell death at higher levels of the cytotoxin compared to 2-D cultures, and appeared to respond to the drug in a manner more comparable to its known activity in vivo. Our results suggest that hepatotoxicity testing using 3-D cultures might be more likely to reflect true physiological responses to cytotoxic compounds than existing models that rely on 2-D culture systems. This technology has potential applications for toxicity testing and drug screening.
Keywords
Adult, Alginates/chemistry, Biocompatible Materials/*chemistry, Cell Count, Cell Culture Techniques/methods, Cells, Cultured, Collagen/analysis/chemistry, Dental Pulp/chemistry/*physiology, Extracellular Matrix/chemistry/*physiology, Fibroblasts/chemistry/cytology, Glucuronic Acid, Hexuronic Acids, Humans, Polyglycolic Acid/*chemistry

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CellLine: HEP-G2
  Morphology: Cancerous-Hepatoma
  Origin: Liver
  Species: Human
Scaffold Form: fibers/mesh
Scaffold Material: PS/ polystyrene