Translational Research in Pharmacology and Toxicology Using Precision-Cut Tissue Slices

Abstract

In this chapter we discuss the application of human liver, intestine, lung and tumour precision-cut tissue slices (PCTS) as a translational ex vivo model in studies on ADME (absorption, distribution, metabolism and excretion) and toxicology of drugs, and for studies on diseases such as fibrosis in the liver and the intestine, obstructive lung diseases, viral infections and cancer. As the use of PCTS in research is steadily increasing it is impossible to give a fully comprehensive review of all applications of PCTS, but by highlighting some of the most important examples with a special emphasis on the application of human PCTS, we aim to show the extensive potential of this versatile technique in pathology and drug research.

Viability, function and morphological integrity of precision-cut liver slices during prolonged incubation: Effects of culture medium

“…The PCLS model is widely used nowadays to study xenobiotic metabolism and toxicity (de Graaf et al, 2007;Groothuis et al, 2014;Vickers and Fisher, 2013). However, most studies have been performed for 24-48 h and no extensive studies have been done to characterize morphological changes observed in the liver slices during prolonged culture time.…”

Glutathione-responsive cyclodextrin-nanosponges as drug delivery systems for doxorubicin: Evaluation of toxicity and transport mechanisms in the liver

“…Recently, several studies have used this technology to study the toxicity and the tissue accumulation mechanisms of different anticancer drugs and supramolecular drug delivery systems (Bertrand et al 2014;Estrada-Ortiz et al 2017;Spreckelmeyer et al 2017;Han et al 2018). Of note, the PCTS system is uniquely suited to examine molecular responses to toxicant exposures and compare species differences, and is nowadays a FDA-approved technology (Groothuis et al 2014).…”

Increased immune cell infiltration in patient-derived tumor explants treated with Traniplatin: an original Pt(iv) pro-drug based on Cisplatin and Tranilast

“…Since TPT displays low cytotoxicity and a reduced platinum uptake in the macrophage cell line RAW 264.7, we hypothesized that a similar biological effect could be observed in patients' tumors using an ex vivo model. 28 We developed a human tumor explants model, which recapitulates in vitro the intra-tumoral heterogeneity -the cancer cells and the tumor microenvironment including inflammatory infiltrate, therefore allowing the evaluation of treatments that might affect both cancer epithelial cells and stromal cells. Briefly, tumor explants, obtained from the surgical specimens of untreated colorectal cancer patients, were cultured ex vivo in the presence of TPT (10 mM) or CDDP (10 mM) for 72 h. The cytotoxicity of the treatment was assessed by detection of the cleaved caspase-3 (a surrogate marker of apoptosis) immunohistochemically in the explants.…”