Hepatocyte hollow-fibre bioreactors: design, set-up, validation and applications

Hepatocytes carry out many vital biological functions, such as synthetic and catabolic reactions, detoxification and excretion. Due to their ability to restore a tissue-like environment, hollow-fibre bioreactors (HFBs) show great potential among the different systems used to culture hepatocytes. Several designs of HFBs have been proposed in which hepatocytes or hepatocyte-derived cell lines can be cultured in suspensions or on a solid support. Currently the major use of hepatocyte HFBs is as bioartificial livers to sustain patients suffering from acute liver failure, but they can also be used to synthesize cell products and as cellular models for drug metabolism and transport studies. Here, we present an overview of the set-up of hepatocyte HFBs and aim to provide potential users with the basic knowledge necessary to develop their own system. First, general information on HFBs is given, including basic principles, transport phenomena, designs and cell culture conditions. The importance of the tests necessary to assess the performance of the HFBs, i.e. the viability and functionality of hepatocytes, is underlined. Special attention is paid to drug metabolism studies and to adequate analytical methods. Finally, the potential uses of hepatocyte HFBs are described.