Liver cell models in in vitro toxicology.

Abstract

In vitro liver preparations are increasingly used for the study of hepatotoxicity of chemicals. In recent years their actual advantages and limitations have been better defined. The cell models, slices, and mainly primary hepatocyte cultures, appear to be the most powerful in vitro systems, as liver-specific functions and responsiveness to inducers are retained either for a few days or several weeks depending on culture conditions. Maintenance of phase and phase 11 xenobiotic metabolizing enzyme activities allows various chemical investigations to be performed, including determination of kinetic parameters, metabolic profile, interspecies comparison, inhibition and induction effects, and drug-drug interactions. In vitro liver cell models also have various applications in toxicology: screening of cytotoxic and genotoxic compounds, evaluation of chemoprotective agents, and determination of characteristic liver lesions and associated biochemical mechanisms induced by toxic compounds. Extrapolation of the results to the in vivo situation remains a matter of debate. Presently, the most convincing applications of liver cell models are the studies on different aspects of metabolism and mechanisms of toxicity. For the future, there is a need for better culture conditions and differentiated hepatocyte cell lines to overcome the limited availability of human liver tissues. In addition, strategies for in vitro analysis of potentially toxic chemicals must be better defined. Environ Health Perspect 106(Suppl 2):511-532 (1998). http.//ehpnetl.niehs.nih.gov/docs/1998/Suppl-2/51 1-532guillouzo/abstract.html

Micromechanical control of cell–cell interactions

“…promotes retention of hepatocyte viability and liver-specific functions that are otherwise rapidly lost in vitro (2). This robust ''coculture'' phenomenon, although poorly understood, has wide-ranging applications in both therapeutic and diagnostic applications of engineered liver tissue (14)(15)(16). Using both conventional techniques and micropatterning approaches, we and others have previously found that the degree of interaction between the two cell types (''heterotypic interaction'') modulated the amount of liver-specific function retained in vitro (2,17).…”

Predictive toxicology using systemic biology and liver microfluidic “on chip” approaches: Application to acetaminophen injury

“…However it is essential use hepatocytes to understand and model metabolic phenomena (Guillouzo, 2008). That is why many tissue engineering processes have been developed to provide better environments for hepatocytes maintenance and development (Gebhardt, 2003;De Bartolo and Bader, 2001;Franklin and Yost, 2000;Guillouzo, 1998;De Kanter et al, 2002). Such environments must reproduce, as closely as possible, the in vivo conditions.…”

Optimization of the isolation and cultivation of Cyprinus carpio primary hepatocytes

“…Since then, use of isolated hepatocytes has provided an ideal system for evaluating many aspects of hepatic metabolism, including biochemical and cellular processes involved in the activation of toxic chemicals and environmental pollutants (Berry et al 1991;Baksi and Frazier 1990;Guillouzo 1998;Kelly et al 1998;Moon et al 1965;Rogiers et al 1995).…”