Precision-Cut Organ Slices as a Tool to Study Toxicity and Metabolism of Xenobiotics with Special Reference to Non-Hepatic Tissues

Abstract

Metabolism of xenobiotics is often seen as an exclusive function of the liver, but some current findings support the notion that the lungs, kidneys and intestine may contribute considerably. After the establishment of the use of liver slices as a useful in vitro model to study metabolism and toxicity of xenobiotics, the same concept is currently being used for slices from lung, kidney and intestine. It is the aim of this review to discuss the use of organ slices in biotransformation research. The basic idea behind the use of tissue slices in biomedical research is the assumption that the cells under study will function optimally in vitro if they are cultivated in an environment that is most alike to their natural in vivo embedding, which is the case in tissue slices. Advantages in the use of organ slices are the relatively easy preparation as well as the potential standardization of both the preparation and use. Moreover, a direct interspecies comparison can be made between liver, lungs, kidneys and intestines, for example with respect to their metabolic capacity and their sensitivity for toxicants. Of major importance is that organ slices can be made with a similar procedure from organs/tissues originating from different species, including man. This latter aspect is useful in drug development in general but also for a better insight in the metabolic fate of compounds in man. Importantly the use of slices may largely contribute to a reduction in the use of experimental animals.

Ex-vivo evaluation of gene therapy vectors in human pancreatic (cancer) tissue slices

“…Other groups have already reported slice culture of various organs from different species [15][16][17]24] . Here, we demonstrated that this technique is also feasible for pancreatic tissue using the Krumdieck tissue slicer.…”

“…Slices can be prepared from several organs including liver, lung, kidney, colon and intestine. They closely resemble the architecture of the original organ, which makes this technique a powerful instrument to perform toxicity and drug-metabolizing studies [15] . Recently, the ultra-thin slices also proved to be a representative model for ex vivo evaluation of the transduction efficiency of adenoviral vectors [16,17] .…”

“…We therefore added ITS, amino acids and vitamins to the culture medium. The oxygen tension varies between culture systems reported [15] . We decided to gas the incubator with 95% O2 to ascertain proper diffusion of oxygen to the inner cell layers.…”

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

“…Human precision-cut lung slices (PCLS), an ex vivo model consisting of all relevant cell types in their microanatomical environment (de Kanter et al, 2002), are well-established in pharmacological testing (Sturton et al, 2008), analysis of allergic immune responses (Wohlsen et al, 2003) and studies of xenobiotic metabolism (Lauenstein et al, 2014). There is also emerging literature concerning the use of ex vivo lung perfusion as a tool for experimental research (Nelson et al, 2014).…”

Interspecies considerations in the evaluation of human food safety for veterinary drugs

“…[33][34][35] Each of these methods has advantages and limitations that will not be covered here. Genomic and proteomic methods also may be useful for exploring interspecies differences in drug metabolizing enzymes.…”