In drug development, in vitro human model systems are absolutely essential prior to the clinical trials,
considering the increasing number of chemical compounds in need of testing, and, keeping in mind that animals
cannot predict all the adverse human health effects and reactions, due to the species-specific differences in metabolic
pathways. The liver plays a central role in the clearance and biotransformation of chemicals and xenobiotics.
In vitro liver model systems by using highly differentiated human cells could have a great impact in preclinical
trials. Membrane biohybrid systems constituted of human hepatocytes and micro- and nano-structured membranes,
represent valuable tools for studying drug metabolism and toxicity. Membranes act as an extracellular
matrix for the adhesion of hepatocytes, and compartmentalise them in a well-defined physical and chemical microenvironment
with high selectivity. Advanced 3-D tissue cultures are furthermore achieved by using membrane
bioreactors (MBR), which ensure the continuous perfusion of cells protecting them from shear stress. MBRs with
different configurations allow the culturing of cells at high density and under closely monitored high perfusion,
similarly to the natural liver. These devices that promote the long-term maintenance and differentiation of primary
human hepatocytes with preserved liver specific functions can be employed in drug testing for prolonged
exposure to chemical compounds and for assessing repeated-dose toxicity. The use of primary human hepatocytes
in MBRs is the only system providing a faster and more cost-effective method of analysis for the prediction of in
vitro human drug metabolism and enzyme induction alternative and/or complementary to the animal experimentation.
In this paper, in vitro models for studying drug metabolism and toxicity as advanced biohybrid membrane
systems and MBRs will be reviewed.
Keywords: Membranes, biohybrid membrane systems, bioreactors, drug testing, liver, human hepatocytes, toxicity.
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