ISSX
Andrew Parkinson (XenoTech LLC, Lenexa, KS, USA) presented his company’s findings in evaluating and subsequently obtaining a license for immortalized human hepatocytes. The hepatocytes were immortalized by scientists from Albert Einstein and Brown Universities, originally as a research effort to develop a liver assist device. They demonstrate remarkably similar morphology to that of fresh human hepatocytes, and their handling, culture, and treatment conditions in induction studies duplicate those for fresh hepatocytes. XenoTech studied the induction of enzymatic activity of four major CYP enzymes (1A2, 2B6, 2C9, and 3A4) following treatment with prototypical inducers, and the magnitude of induction was comparable to the median induction seen in fresh human hepatocytes as described in a paper published in Drug Metabolism and Disposition in 2003 and authored by, among others, XenoTech scientists. For example, the immortalized cells demonstrated 20 and 5-fold induction of 1A2 and 3A4 activity respectively, while median induction in fresh human hepatocytes for the same CYP’s was 8 and 4-fold. Reproducibility of induction was superior to that in fresh human hepatocytes, and the specificity of response to different chemicals matched that of fresh human hepatocytes. Other scientists have also evaluated the cells and their findings also support the use of the cells for induction studies. XenoTech is in the final stages of confirming the cells’ suitability for metabolism and hepatotoxicity studies, and expects the immortalized hepatocytes to offer convenience, reproducibility, and long-term data comparisons that will alleviate many of the well-known limitations and difficulties of using non-immortalized human hepatocytes.
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