From Bench to Slice: Exploring Viability and Nanoparticle Uptake in Precision-Cut Liver Slices (PCLS) as a Basic Research Model

Abstract

Translational research plays a crucial role in bridging the gap between scientific discoveries and clinical applications. However, the translation of research findings into clinically implementable therapies often faces significant challenges, resulting in limited clinical impact despite substantial investments in medical research. Herein an alternative for animal research, precision-cut liver slices (PCLS) an ex vivo mode is explored. This model could lower animal use and so lowering the ethical and fiscal cost of research while breaching the gap between the lab and the clinic. PCLS provide a valuable platform for studying liver-related research questions and pre-screening drugs before moving to in vivo or clinical experiments. Here we present a protocol for generating PCLS using a vibratome. This was done by puncturing 8mm murine livers, embedding them into low-gelling agarose, and cutting in 300 μm slices. The PCLS were cultured ex vivo for up to 4 days and viability was evaluated using MTS assay. Pilot experiments with fluorescently labelled liposomes were added to the PCLS to explore the effects of nanoparticles on the liver, which was analysed by flow cytometry. Our report includes the experimental workflow for using PCLS as an ex vivo research model and discusses optimizations required for improving PCLS viability.