title: Evaluation of drug-induced injury and human response in precision-cut tissue slices.
abstract: 1.Drug induced organ injury is multifaceted, encompassing a spectrum of cell types and numerous networks reflecting cell-cell and cell-matrix interactions. Characterization of drug induced side effects and human response can be addressed in organ slice models. 2.The application of human tissue to various organ slice models including liver, intestine, kidney, liver-blood co-cultures and thyroid enhances our ability to focus on the clinical relevance of side effects identified in animal studies for human, and to evaluate potential biomarkers of the side effects. Dose-response relationships can help discern drug concentrations which alter organ function or affect morphology, to identify drug concentrationswhich could pose a risk for humans. 3.Insight into pathways of organ injury, by incorporating gene and protein expression profiling, with functional measurements and morphology, aid to define species differences and sensitivity. 4.Human organ slice studies are valuable for bridging the extrapolation of animal derived data and for identifying mechanisms relevant for humans, thereby expanding the scope of translational research for drug safety assessment.
authors.affiliation: Drug Safety Evaluation, Allergan Inc., Irvine, CA 92623, USA. vickers_alison@allergan.com
authors.forename: Alison E M
authors.initials: AE
authors.lastname: Vickers
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Fisher
mesh_terms: D000818:Animals; D054316:Biomarkers, Pharmacological / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008954:Models, Biological; D009924:Organ Culture Techniques / Q000379:methods
chemical_list: D054316:Biomarkers, Pharmacological