Liver organoid as a 3D in vitro model for drug validation and toxicity assessment

Anastasia Brooks; Xiaowen Liang; Yonglong Zhang; Chun-Xia Zhao; Michael S Roberts; Haolu Wang; Lei Zhang; Darrell H G Crawford

doi:10.1016/j.phrs.2021.105608

Liver organoid as a 3D in vitro model for drug validation and toxicity assessment

Pharmacol Res. 2021 Jul:169:105608. doi: 10.1016/j.phrs.2021.105608. Epub 2021 Apr 20.

Authors

Anastasia Brooks¹, Xiaowen Liang², Yonglong Zhang³, Chun-Xia Zhao⁴, Michael S Roberts⁵, Haolu Wang², Lei Zhang⁶, Darrell H G Crawford⁷

Affiliations

¹ The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Australia; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD, Australia.
² The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Australia; Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, QLD, Australia.
³ State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
⁴ Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD, Australia.
⁵ The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Australia; School of Pharmacy and Medical Science, University of South Australia, Adelaide, Australia.
⁶ State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. Electronic address: rayzhang@sibcb.ac.cn.
⁷ Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, QLD, Australia; School of Clinical Medicine, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia. Electronic address: d.crawford@uq.edu.au.

PMID: 33852961
DOI: 10.1016/j.phrs.2021.105608

Abstract

The past decade has seen many advancements in the development of three-dimensional (3D) in vitro models in pharmaceutical sciences and industry. Specifically, organoids present a self-organising, self-renewing and more physiologically relevant model than conventional two-dimensional (2D) cell cultures. Liver organoids have been developed from a variety of cell sources, including stem cells, cell lines and primary cells. They have potential for modelling patient-specific disease and establishing personalised therapeutic approaches. Additionally, liver organoids have been used to test drug efficacy and toxicity. Herein we summarise cell sources for generating liver organoids, the advantages and limitations of each cell type, as well as the application of the organoids in modelling liver diseases. We focus on the use of liver organoids as tools for drug validation and toxicity assessment.

Keywords: Drug validation; Liver organoid; Toxicity assessment.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Humans
Liver / cytology
Liver / drug effects*
Liver Diseases / drug therapy
Liver Neoplasms / drug therapy
Organoids / drug effects*
Toxicity Tests / methods*
Treatment Outcome