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DOI: 10.1055/a-1934-5588
Three-Dimensional Organoids as a Model to Study Nonalcoholic Fatty Liver Disease
Funding This work was partially supported by ASTS Faculty Development Grant (BE), Indiana University Health Values Fund for Research Award (VFR-457-Ekser) (BE), and IU Health Foundation Jerome A. Josephs Fund for Transplant Innovation Grant (BE), the Hickam Endowed Chair, Gastroenterology, Medicine, Indiana University, the Indiana University Health – Indiana University School of Medicine Strategic Research Initiative, the Senior Research Career Scientist Award (IK6 BX004601) and the VA Merit award (5I01BX000574) to GA and the Research Career Scientist Award (IK6BX005226) and the VA Merit award (1I01BX003031) to HF, and Career Development Award (1IK2BX004306) to LK from the United States Department of Veteran's Affairs, Biomedical Laboratory Research and Development Service and NIH grants DK108959 and DK119421 (HF), DK054811, DK115184, DK076898, DK107310, DK110035, DK062975 and AA028711 (GA) and the PSC Partners Seeking a Cure (GA). Portions of these studies were supported by resources at the Richard L. Roudebush VA Medical Center, Indianapolis, IN. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs.
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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.
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.
Publikationsverlauf
Accepted Manuscript online:
31. August 2022
Artikel online veröffentlicht:
14. Oktober 2022
© 2022. Thieme. All rights reserved.
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