Application of Short‐ and Long‐Term Hepatocyte Cultures to Predict Toxicities

Tuschl, Gregor; Hrach, Jens; Hewitt, Philip; Mueller, Stefan O.

doi:10.1002/9780470516751.ch7

Cited by 5 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Extensive reviews have been published on conditions to improve hepatocyte survival and function in vitro (8)(9)(10)(11)(12)(13). Very early it appeared that several factors were critical for survival and function of hepatocytes in primary culture, they included soluble factors (i.e., medium composition) and pericellular environmental factors (matrix proteins as well as other cell types).…”

Section: Primary Adult Hepatocytesmentioning

confidence: 99%

“…In vitro chronic toxicity remains a matter of debate and only few studies have been published, using primary hepatocytes maintained in conditions that increase their survival and better preserve their functions, e.g., in culture with another cell type (105) or in a sandwich configuration (13). These studies have shown that toxicity usually occurred with lower drug concentrations after reiterated exposure.…”

Section: Cellular Toxicitymentioning

confidence: 99%

See 1 more Smart Citation

General Review on In Vitro Hepatocyte Models and Their Applications

Guguen‐Guillouzo

Guillouzo

2010

Methods in Molecular Biology

205

137

View full text Add to dashboard Cite

In vitro hepatocyte models represent very useful systems in both fundamental research and various application areas. Primary hepatocytes appear as the closest model for the liver in vivo. However, they are phenotypically unstable, have a limited life span and in addition, exhibit large interdonor variability when of human origin. Hepatoma cell lines appear as an alternative but only the HepaRG cell line exhibits various functions, including major cytochrome P450 activities, at levels close to those found in primary hepatocytes. In vitro hepatocyte models have brought a substantial contribution to the understanding of the biochemistry, physiology, and cell biology of the normal and diseased liver and in various application domains such as xenobiotic metabolism and toxicity, virology, parasitology, and more generally cell therapies. In the future, new well-differentiated hepatocyte cell lines derived from tumors or from either embryonic or adult stem cells might be expected and although hepatocytes will continue to be used in various fields, these in vitro liver models should allow marked advances, especially in cell-based therapies and predictive and mechanistic hepatotoxicity of new drugs and other chemicals. All models will benefit from new developments in throughput screening based on cell chips coupled with high-content imaging and in toxicogenomics technologies.

show abstract

Section: Primary Adult Hepatocytesmentioning

confidence: 99%

Section: Cellular Toxicitymentioning

confidence: 99%

General Review on In Vitro Hepatocyte Models and Their Applications

Guguen‐Guillouzo

Guillouzo

2010

Methods in Molecular Biology

205

137

View full text Add to dashboard Cite

show abstract

“…Primary human hepatocytes but also permanent cells have been successfully employed for that purpose (Tuschl et al, 2007).…”

Section: In Vitro Methodsmentioning

confidence: 99%

“…However, primary hepatocytes are useful tools to assess compounds that require metabolic activation. Furthermore, long-term hepatocyte cultures can be used to assess effects after repeated dosing (Tuschl and Mueller, 2006;Tuschl et al, 2007). In addition, permanent cell lines with high metabolic capacity are now becoming available that could be employed as replacements for primary hepatocytes (Aninat et al, 2006;Ripp et al, 2006).…”

Section: Selection Of Cell Typesmentioning

confidence: 99%

“…Therefore, delayed toxic actions may only be detected by in vitro assays with extended incubation periods. It is thus advisable to compare different incubation times for unknown compounds in order to gain realistic evidence on the acute oral toxicity risk (Ukelis, 2005;Tuschl et al, 2007). Furthermore, analysis after a treatment free period could be used to assess the reversibility of toxic effects in vitro similar to repeat-dose toxicity studies.…”

Section: Selection Of Incubation Timementioning

confidence: 99%

See 1 more Smart Citation