Hepatocyte cultures in drug metabolism and toxicological research and testing.
When a new chemical entity is tested for its safety for humans and their environment, in vivo experiments on living animals are usually conducted. However, in the early preclinical stage of drug development, in vitro techniques, and more specifically hepatocyte-based in vitro models, are currently being applied. A major problem, however, related to the use of hepatocytes and their cultures is their limited viability, which is associated with the loss of phase I and phase II biotransformation capacity. Therefore, in order to keep the hepatocytes functional for a longer period, the in vivo microenvironment is mimicked in vitro as closely as possible through the addition of soluble medium components, coculture with helper cells, or culture on an extracellular matrix (sandwich culture). We discuss the advantages and disadvantages of current short- and long-term hepatocyte culture systems are discussed as well as their proper use in toxicological research and testing.
Vanhaecke
Tamara
T
Department of Toxicology, Vrije Universiteit Brussel, Belgium.
Rogiers
Vera
V
D001711:Biotransformation; D002478:Cells, Cultured; D018920:Coculture Techniques; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D010599:Pharmacokinetics; D018675:Toxicity Tests