{"doi":"10.1111/jvp.13255","title":"O89 | A novel biologically relevant canine in vitro model for the study of intestinal inflammation","abstract":"Introduction: Preclinical evaluation of novel drug candidates currently relies on conventional 2D cell lines, such as Caco-2 cells for the intestine. However, the inherent lack of complexity of these systems often fails to accurately model the in vivo pharmacological effects of therapeutic drugs. In this proof-of-concept study, we utilized canine adult stem cell-derived colonoids in the Transwell™ system to model in vivo inflammation induced by TNF-α and subsequently assessed the inhibitory effect of dexamethasone on the inflammatory response. Materials and Methods: After expansion, 3D canine colonoids previously characterized extensively by our group, were dissociated and seeded on Transwell™ inserts. TEER values were recorded to monitor monolayer integrity. When TEER values plateaued, expansion media was exchanged for differentiation media, and TNF-α was added to either the apical or basal chamber at 0, 0.5, 1, 2.5, 5, or 10 ng/mL. After 24 h, supernatants were collected for IL-8 quantification using a commercial ELISA immunoassay. In the subsequent experiment, 1, 10, or 100 μM dexamethasone was added apically in the presence or absence of 5 ng/mL basal TNF-α. Results: Cell confluence was achieved within 10 days of culture with TEER values peaking at ~4000 Ω.cm2 at steady state. After 24 h, apical or basolateral TNF-α both increased apical IL-8 secretion in a dose-dependent manner until reaching a maximum of ~15,000 pg/mL (at 2.5 ng/mL TNF-α). With apical TNF-α stimulation, basal secretion of IL-8 continued to increase until reaching a maximum of ~350 pg/mL (at 10 ng/mL). The largest reduction of IL-8 in the apical chamber was observed at the 4-h timepoint with 10 μM of dexamethasone. Conclusions: Development of a physiologically relevant canine model of intestinal inflammation is a critical step towards improved in vitro predictability of drug preclinical efficacy and safety. Here we established proof-of-concept that canine colonoids could provide a reliable model to evaluate drug candidates with predicted anti-inflammatory efficacy in the intestine. Acknowledgements: Funding was provided by 3D Health Solutions Inc., Ames, USA, Christian Hansen Holding, Denmark, and a donation from the ISU Foundation.","journal":"Journal of Veterinary Pharmacology and Therapeutics","year":2023,"id":408476,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9411,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T01:21:18.414003Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}