Three-Dimensional Organoids as a Model to Study Nonalcoholic Fatty Liver Disease

Abstract

Despite the rising prevalence of nonalcoholic fatty liver disease (NAFLD), the underlying disease pathophysiology remains unclear. There is a great need for an efficient and reliable “human” in vitro model to study NAFLD and the progression to nonalcoholic steatohepatitis (NASH), which will soon become the leading indication for liver transplantation. Here, we review the recent developments in the use of three-dimensional (3D) liver organoids as a model to study NAFLD and NASH pathophysiology and possible treatments. Various techniques that are currently used to make liver organoids are discussed, such as the use of induced pluripotent stem cells versus primary cell lines and human versus murine cells. Moreover, methods for inducing lipid droplet accumulation and fibrosis to model NAFLD are explored. Finally, the limitations specific to the 3D organoid model for NAFLD/NASH are reviewed, highlighting the need for further development of multilineage models to include hepatic nonparenchymal cells and immune cells. The ultimate goal is to be able to accurately recapitulate the complex liver microenvironment in which NAFLD develops and progresses to NASH.

Keywords

NAFLD - NASH - human liver organoids - 3D cell culture

Authors' Contribution

Y.P. drafted the first manuscript, D.T. and I.B. helped with writing and reviewing the literature. B.E. and W.Z. initiated the concept and assisted in writing and critically reviewing the literature. All authors critically reviewed and participated in the writing of the paper. All authors approved the final version.

^* These senior authors contributed equally to the study.

Publication History

Accepted Manuscript online:
31 August 2022

Article published online:
14 October 2022

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