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To survive for more than a few hours, hepatocytes must attach to a support When cultured under conventional conditions they form a monolayer that usually survrves for about 1 week. However, the hepatocytes undergo phenotypic changes, including dedifferentiation and the selective loss of some key pathways of xenobiotic metabolism (
see
Chapter 30). The use of more sophisticated culture techniques, such as coculture of rat hepatocytes with rat liver epithelial cells (RLEC) of primitive biliary origin, that more closely mimic the situation in viva results in a longer survival time and better maintenance of drug-metabolizing capacity (
see
Chapter 30). Both culture techniques are described here in detail. They are based on the work of Guguen-Guillouzo (
1
), Guillouzo (
2
), and Williams et al. (
5
).