Viability and Functionality of Liver Slices

Finally, inter-laboratory standardization of incubation systems and culture media would increase the validity of comparisons made between results from different laboratories. 

For pharmacological, toxicological and transport studies it is of utmost importance to assess not only the viability but also the functionality of the liver slices. This is essential both for end-point determination of toxic cell damage, and to assess the quality of the tissue during in- 

12 Use of Human Tissue Slices in Drug Targeting Research 

Because these different viability tests all reflect different aspects of cell viability, the choice of test depends on the aim of the study. For toxicity studies where biotransformation is an important bioactivation or detoxification step, metabolic function tests should be included to judge the validity of the method, whereas viability tests are needed to assess toxic effects. Both positive and negative controls should be included in such studies. When human liver is used, the characterization of metabolic activity is especially important because of the large inter-individual variability associated with this property [75]. 

The viability and function tests described above are used to evaluate the hepatocytes within the slice. Up to now, tests to measure the viability of the non-parenchymal cells have not been reported. The presence of the latter cell types is one of the conceptual advantages of slices as compared to isolated hepatocytes. As some drug targeting devices are designed to target non-parenchymal cells in the liver, the development of tests for the sinusoidal cell types deserves more attention. For example, the uptake of substrates such as succinylated human serum albumin (Suc-HSA,which is specifically endocytosed by endothelial cells [79]), or hyaluronic acid [80], can be used to assess the functionality of endocytotic pathways in the endothelial cells in the liver [81]. Other modified proteins that are specifically taken up by Kupffer cells such as mannosylated HSA, may be used to assess the functionality of the endocytotic pathway in Kupffer cells [79]. Another parameter which can be used to assess the functionality of these non-parenchymal liver cells, is the excretion of cytokines in response to pro-inflammatory stimuli. Non-parench5mal cell function in liver slices will be described in more detail in the Section 12.7. 

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