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P1006
Hepatocyte Culture Performance is Improved Over Current Methods When Cells are Grown On A Synthetic ECM-Mimetic Surface Topography
Presenter Michael Briggs, Corning Life Sciences, USA
Additional Authors: Mark Rothenberg, Fawad Faruqi, James J. Cali, Mary Sobol, Jeffrey Ross, and Todd Upton
Oxidative metabolism by cytochrome P450 liver enzymes is a primary method of drug metabolism, making drugs more water soluble so they can be more easily excreted from the body. Enzyme induction occurs when one drug stimulates production of more enzymatic metabolism capacity. Fluorescence, luminescence and LC/MS based CYP metabolism assays have been developed and are widely used in the pharmaceutical industry to screen and monitor the efficacy of test compounds. CYP1A2 and CYP3A4 are two of the most common CYP isoforms used to monitor drug metabolism.
Human primary hepatocytes are the cells of choice to conduct CYP metabolism studies; however, they rapidly lose their metabolic activity upon plating on a two-dimensional cell culture surface. Any technology (cell surface, vessel, growth medium or combinations thereof) that allows the cells to maintain their normal metabolic functions for longer time periods will be of a great importance to the pharmaceutical industry.In this work, we assessed the functional performance of hepatocytes derived from various sources (rat primaries, HepG2, Fa2N-4 cell lines) against various assay readouts, both for CYP activity and expression, and for hepatocyte cell function. CYP1A2 and CYP3A4 activity (via P450-Glo assay) and expression (via reverse transcription) were assessed, along with cell functional readouts that included membrane integrity, mitochondrial function and oxidative stress. We determined that cell culture surfaces possessing a novel synthetic ECM-like topography can replace or even outperform standard biologically-coated surfaces for selected hepatocyte assays.