Commonly used organoid culture media prevent ferroptosis

Abstract

Organoids enable the recreation of organ physiology in vitro and serve as powerful models for biology in basic life science research and drug discovery and development. However, organoid culture requires complex media formulations that include antioxidants, potentially confounding experimental results sensitive to such conditions. Here we report that the growth conditions used commonly to generate organoid models inhibit ferroptosis, an iron-dependent form of lipid peroxidative cell death with relevance to human disease, thus rendering such models incompatible with ferroptosis research. We identify medium components that diminish or eliminate ferroptosis sensitivity and outline strategies for avoiding anti-ferroptotic culture conditions in organoid and other cell culture applications. These findings provide a roadmap for adapting organoid models for the study of ferroptosis and leveraging their strengths for advancing ferroptosis-modulating therapeutics.