Revolutionizing liver fibrosis research: the promise of 3D organoid models in understanding and treating chronic liver disease

INTRODUCTION: Liver fibrosis, marked by excessive extracellular matrix deposition, is a significant consequence of chronic liver injuries from various conditions. It can progress to end-stage liver disease, with liver transplantation often being the only treatment option. Recent advancements in 3D-organoid technology have transformed liver disease research by providing models that mimic the human liver's physiological environment, offering insights into mechanisms of fibrosis and potential therapies. AREAS COVERED: This report highlights cellular and molecular factors leading to liver fibrosis and the limitations of 2D in vitro models in replicating complex liver dynamics. It emphasizes the advantages of 3D-liver organoids as promising tools for advancing research and drug discovery, providing greater accuracy than traditional models. Additionally, it discusses recent advancements in the development and future applications of liver organoids in fibrosis research. EXPERT OPINION: Liver organoids currently lack cellular diversity and essential features such as vascular, neuronal, microbiome, and immune responses, limiting their effectiveness in mature fibrosis models. Addressing these shortcomings through bioengineering advancements and emerging technologies like CRISPR/Cas9 will enhance the utility of liver organoids.