Precision-cut tissue slice assay to advance drug discovery 2277

Abstract Description Precision-cut tissue slices (PCTS) serves as an effective ex vivo model for studying human diseases. PCTS retain the complex tissue microenvironment including immune components and the extracellular matrix, rendering them a valuable tool for drug discovery. We have successfully established ex vivo anti-fibrotic and anti-Inflammation models using precision cut liver slices (PCLS) from rats. Following treatment with TGF-β for 24h, mRNA levels of IL-6, TNF-α, COL1A1, α-SMA, TGF-β1, IL-1β, etc., significantly increased compared with untreated PCLS controls. However, these changes were downregulated upon treatment with SB525334, Nintedanib, or Dexamethasone. Moreover, upon LPS induction, mRNA levels of IL-6, TNF-α, COL1A1, α-SMA, TGF-β1, IL-1β, IL-10, CTGF and iNOS significantly increased. Tacrolimus and Baricitinib significantly decreased LPS-induced upregulation of these inflammation genes. Treatment responses can be assessed using multiple readouts, including tissue viability, RNA and protein analyses, histology, and live-cell imaging. These readouts enhance PCTS’s potential as a translational tool, bridging in vitro assay findings with in vivo efficacy. Ongoing studies showed promising results for advancing drug discovery. Funding Sources In Vivo Pharmacology Unit, WuXi Biology, WuXi AppTec, China Topic Categories Technological Innovations in Immunology (TECH)