Recent advances in liver organoids and their use in in vitro modeling of non-alcoholic fatty liver disease

Abstract

The liver is involved in physiological activities critical for survival. Chronic liver disease (CLD) frequently progresses to life-threatening liver failure, as evidenced by CLD patients’ high morbidity and mortality rates. Over the years, non-alcoholic fatty liver disease (NAFLD) has received significant attention as an etiology of CLD given its increasing prevalence and progression towards severe pathological conditions such as fibrosis. To answer the urgent need for effective therapeutics that treat CLD, an advanced cellular model, the liver organoid, is used to model and study the complex pathophysiology of NAFLD. Liver organoids recapitulate in vivo aspects of liver tissue such as 3-dimensional cell-cell and cell-extracellular matrix interactions and biomolecular gradients. Moreover, liver organoids can be readily generated from patient-specific liver tissues and induced pluripotent stem cells, enabling their use in a wide range of personalized clinical applications. In recent research, numerous attempts have been made to establish multicellular liver organoids capable of modeling disease phenotypes that involve parenchymal and non-parenchymal liver cells. In this review, we focus on recent advances in liver organoids and highlight the applicability of organoids for modeling NAFLD within the context of cellular sources and composition.