1. Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China.
2. International Healthcare Innovation Institute (Jiangmen), Jianghai, Jiangmen, Guangdong Province, China.
3. Research and Development, Qingdao Haier Biotech Co. Ltd, Qingdao, China.
4. Guangdong ORGANOID Biotechnology Co. Ltd, Jiangmen, China.
5. Department of Surgery, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.
6. Department of Life Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
7. Department of Stem Cell and Regenerative Biotechnology, The institute of advanced regenerative science, Konkuk University, Seoul, Republic of Korea.
*These authors contributed equally to this work.
Non-alcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH) have presented a major and common health concern worldwide due to their increasing prevalence and progressive development of severe pathological conditions such as cirrhosis and liver cancer. Although a large number of drug candidates for the treatment of NASH have entered clinical trial testing, all have not been released to market due to their limited efficacy, and there remains no approved treatment for NASH available to this day. Recently, organoid technology that produces 3D multicellular aggregates with a liver tissue-like cytoarchitecture and improved functionality has been suggested as a novel platform for modeling the human-specific complex pathophysiology of NAFLD and NASH. In this review, we describe the cellular crosstalk between each cellular compartment in the liver during the pathogenesis of NAFLD and NASH. We also summarize the current state of liver organoid technology, describing the cellular diversity that could be recapitulated in liver organoids and proposing a future direction for liver organoid technology as an in vitro platform for disease modeling and drug discovery for NAFLD and NASH.
Keywords: non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), liver organoids, disease modeling, drug discovery