Cell-based models to predict human hepatotoxicity of drugs
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| Format: | Artículo científico |
| Language: | en |
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Asociación Española de Toxicología
2014
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| _version_ | 1876482075416068096 |
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| author | MJ Gómez-Lechón |
| author_facet | MJ Gómez-Lechón |
| contents | Cell-based models to predict human hepatotoxicity of drugs MJ Gómez-Lechón L Tolosa Donato MT Medicina Co CYP culture scaffold spheroids Drug-induced liver injury is a significant leading cause of liver disease and post-market attrition of approved drugs. Several hepatic cell-based models have been used for early safety risk assessment during drug development. Their capacity to predict hepatotoxicity depends on cells' functional performance. Cultured hepatocytes have contributed to increase knowledge of the metabolic patterns and mechanisms involved in drug toxicity. A major limitation of monolayer hepatocytes is that they undergo rapid loss of hepatic functionality over time, particularly drug metabolising capability. The sandwich culture model promotes polarised cell surface and stabilises hepatocyte functionality, particularly transport systems, better than monolayer cultures. As 3D spatial organisation and complex heterotypic cell interactions are essential for the functional homeostasis of the liver, hepatocyte models (3D cultures, co-cultures with NPCs and microfluidic systems) that mimic cell-cell, cellmatrix interactions and nutrient flow characteristic of the liver microenvironment have been shown to improve the metabolic competency of hepatocytes and have been proposed for better in vitro predictions of drug hepatotoxicity. In addition to hepatocytes, other cell-based models have been proposed for hepatotoxicity studies. Hepatoma cell lines are metabolically poor compared to hepatocytes, but offer key advantages, such as unlimited life span, reproducibility, high availability and easy handling, which make them useful for screening purposes. Alternatively, hepatic cell lines engineered for stable or transient expression of key drug-metabolising enzymes have also been used. Finally, stem cell-derived hepatocytes are emerging in vitro systems that would provide a stable source of hepatocytes from individuals with highly valuable particular polymorphic characteristics for preclinical drug metabolism and toxicity prediction of new drugs. 2014 artículo científico 0212-7113 https://www.redalyc.org/articulo.oa?id=91932969007 en http://www.redalyc.org/revista.oa?id=919 Revista de Toxicología application/pdf Asociación Española de Toxicología Revista de Toxicología (España) Num.2 Vol.31 |
| format | Artículo científico |
| id | redalyc_91932969007 |
| institution | Redalyc |
| language | en |
| publishDate | 2014 |
| publisher | Asociación Española de Toxicología |
| spellingShingle | Cell-based models to predict human hepatotoxicity of drugs MJ Gómez-Lechón Medicina Co CYP culture scaffold spheroids Cell-based models to predict human hepatotoxicity of drugs MJ Gómez-Lechón L Tolosa Donato MT Medicina Co CYP culture scaffold spheroids Drug-induced liver injury is a significant leading cause of liver disease and post-market attrition of approved drugs. Several hepatic cell-based models have been used for early safety risk assessment during drug development. Their capacity to predict hepatotoxicity depends on cells' functional performance. Cultured hepatocytes have contributed to increase knowledge of the metabolic patterns and mechanisms involved in drug toxicity. A major limitation of monolayer hepatocytes is that they undergo rapid loss of hepatic functionality over time, particularly drug metabolising capability. The sandwich culture model promotes polarised cell surface and stabilises hepatocyte functionality, particularly transport systems, better than monolayer cultures. As 3D spatial organisation and complex heterotypic cell interactions are essential for the functional homeostasis of the liver, hepatocyte models (3D cultures, co-cultures with NPCs and microfluidic systems) that mimic cell-cell, cellmatrix interactions and nutrient flow characteristic of the liver microenvironment have been shown to improve the metabolic competency of hepatocytes and have been proposed for better in vitro predictions of drug hepatotoxicity. In addition to hepatocytes, other cell-based models have been proposed for hepatotoxicity studies. Hepatoma cell lines are metabolically poor compared to hepatocytes, but offer key advantages, such as unlimited life span, reproducibility, high availability and easy handling, which make them useful for screening purposes. Alternatively, hepatic cell lines engineered for stable or transient expression of key drug-metabolising enzymes have also been used. Finally, stem cell-derived hepatocytes are emerging in vitro systems that would provide a stable source of hepatocytes from individuals with highly valuable particular polymorphic characteristics for preclinical drug metabolism and toxicity prediction of new drugs. 2014 artículo científico 0212-7113 https://www.redalyc.org/articulo.oa?id=91932969007 en http://www.redalyc.org/revista.oa?id=919 Revista de Toxicología application/pdf Asociación Española de Toxicología Revista de Toxicología (España) Num.2 Vol.31 |
| title | Cell-based models to predict human hepatotoxicity of drugs |
| topic | Medicina Co CYP culture scaffold spheroids |
| url | https://www.redalyc.org/articulo.oa?id=91932969007 |