A membrane-based small-scale bioreactor for accelerated in vitro drug screenings with primary hepatocytes

Abstract

The use of primary hepatocyte cultures is well established for the study of drug metabolism and drug-drug interactions. However, the application of these cells in hybrid artificial liver systems has been hampered by the gradual loss of differentiated function in vitro. Therefore, several hepatic culture systems have been developed to circumvent this problem. In the present study, a small-scale bioreactor with a gas-permeable membrane was constructed in which primary hepatocytes were cultured in a sandwich model. The cells could preserve their specific functions such as protein synthesis, detoxification, and biotransformation when cultured in the bioreactor. Compared to the conventional well cultures, the use of the mini bioreactor has the benefit of promoting oxygen-dependent processes such as urea synthesis and Phase I biotransformation and of allowing induction of Phase I enzymatic activities by drugs.