Hepatocyte differentiation.

Methods in Molecular Biology
Katy M Olsavsky GoyakCurtis J Omiecinski

Abstract

Increasingly, research suggests that for certain systems, animal models are insufficient for human toxicology testing. The development of robust, in vitro models of human toxicity is required to decrease our dependence on potentially misleading in vivo animal studies. A critical development in human toxicology testing is the use of human primary hepatocytes to model processes that occur in the intact liver. However, in order to serve as an appropriate model, primary hepatocytes must be maintained in such a way that they persist in their differentiated state. While many hepatocyte culture methods exist, the two-dimensional collagen "sandwich" system combined with a serum-free medium, supplemented with physiological glucocorticoid concentrations, appears to robustly maintain hepatocyte character. Studies in rat and human hepatocytes have shown that when cultured under these conditions, hepatocytes maintain many markers of differentiation including morphology, expression of plasma proteins, hepatic nuclear factors, phase I and II metabolic enzymes. Functionally, these culture conditions also preserve hepatic stress response pathways, such as the SAPK and MAPK pathways, as well as prototypical xenobiotic induction responses. This c...Continue Reading

Citations

Dec 17, 2015·Expert Opinion on Drug Metabolism & Toxicology·R J RileyB Williamson
Jun 4, 2016·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Akinori TakemuraKousei Ito
Dec 31, 2016·Pharmaceutics·Elodie JouanOlivier Fardel
Jun 28, 2013·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Alessandra StampellaMariella Dentini
Mar 10, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Sreenivasa C RamaiahgariStephen S Ferguson
Aug 8, 2021·Cancers·Alexandru BlidiselOctavian Marius Cretu

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