NTP optimizes liver model for improved toxicity screening
National Toxicology Program scientists have recently developed a novel way of culturing liver cells to vastly improve modeling of the human liver. Because the liver plays a vital role in how the body processes and eliminates drugs and other chemicals, models that reflect its complex physiology are in high demand. In this new process, three-dimensional (3D) HepaRG liver cells were grown in spheroid structures that more closely resemble the architecture of the human liver. This approach will allow for more effective screening of chemicals with the potential to cause liver toxicity.
Although liver models have improved substantially in recent years, they fail to reliably predict liver toxicity due to various factors, including poor differentiation, limited lifespan in cell culture, and accurate representation of the expression and function of drug metabolizing enzymes. This new 3D HepaRG spheroid model was tested rigorously for these parameters. It was found to be a cost-effective and user-friendly way to achieve consistency and maintain the cultured cells for a toxicity screening.
The model also maintains drug metabolizing activity, which is key for predicting metabolism-dependent toxicities. Finally, this model accurately reflected the liver toxicity of several chemicals that are known to cause liver toxicity in humans. For example, it distinguished liver-toxic troglitazone and trovafloxacin from the safer analogues rosiglitazone and levofloxacin, respectively. (AD)
Citation: Ramaiahgari SC, Waidyanatha S, Dixon D, DeVito MJ, Paules RS, Ferguson SS. 2017. From the Cover: Three-dimensional (3D) HepRG spheroid model with physiologically relevant xenobiotic metabolism competence and hepatocyte functionality for liver toxicity screening. Toxicol Sci 159(1):124–136.