From gut to liver: organoids as platforms for next-generation toxicology assessment vehicles for xenobiotics

Abstract

Traditional toxicological assessment relied heavily on 2D cell cultures and animal models of study, which were inadequate for the precise prediction of human response to chemicals. Researchers have now shifted focus on organoids for toxicological assessment. Organoids are 3D structures produced from stem cells that mimic the shape and functionality of human organs and have a number of advantages compared to traditional models of study. They have the capacity to replicate the intricate cellular microenvironment and in vivo interactions. They offer a physiologically pertinent platform that is useful for the researchers to monitor cellular responses in a more realistic manner and evaluate drug toxicity. Additionally, organoids can be created from cells unique to a patient, allowing for individualized toxicological research and providing understanding of the inter-individual heterogeneity in drug responses. Recent developments in the use of gut and liver organoids for assessment of the xenobiotics (environmental toxins and drugs) is reviewed in this article. Gut organoids can reveal potential damage to the digestive system and how xenobiotics affect nutrient absorption and barrier function. Liver is the primary site of detoxification and metabolism of xenobiotics, usually routed from the gut. Hence, these are linked and crucial for evaluating chemical or pollutant induced organ toxicity, forecasting their metabolism and pharmacokinetics. When incorporated into the drug development process, organoid models have the potential to improve the accuracy and efficiency of drug safety assessments, leading to safer and more effective treatments. We also discuss the limitations of using organoid-based toxicological assays, and future prospects, including the need for standardized protocols for overcoming reproducibility issues.

Topics & Concepts