Review
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Aug 26, 2019; 11(8): 535-547
Published online Aug 26, 2019. doi: 10.4252/wjsc.v11.i8.535
Derivation and applications of human hepatocyte-like cells
Shuang Li, Shi-Qian Huang, Yong-Xu Zhao, Yu-Jie Ding, Dan-Jun Ma, Qiu-Rong Ding
Shuang Li, Shi-Qian Huang, Yong-Xu Zhao, Qiu-Rong Ding, CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Yong-Xu Zhao, Dan-Jun Ma, College of Mechanical Engineering, Dongguan University of Technology, Dongguan 523808, Guangdong Province, China
Yu-Jie Ding, Department of Pharmacy, Mudanjiang Kang’an Hospital, Mudanjiang 157011, Heilongjiang Province, China
Qiu-Rong Ding, Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
Author contributions: Li S, Ma DJ and Ding QR contributed to conceptualization; Li S contributed to original draft preparation; Huang SQ, Zhao YX, Ding YJ, Ma DJ and Ding QR contributed to review and editing.
Supported by National Key RD Program of China, No. 017YFA0102800; and No. 2017YFA0103700; the National Natural Science Foundation of China, No. 31670829.
Conflict-of-interest statement: None of the authors have any conflicts of interest relevant to this study.
Open-Access: This is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Qiu-Rong Ding, PhD, Professor, CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. qrding@sibs.ac.cn
Telephone: +86-21-54920998 Fax: +86-21-54920078
Received: February 16, 2019
Peer-review started: February 18, 2019
First decision: May 9, 2019
Revised: June 15, 2019
Accepted: July 29, 2019
Article in press: July 29, 2019
Published online: August 26, 2019
Abstract

Human hepatocyte-like cells (HLCs) derived from human pluripotent stem cells (hPSCs) promise a valuable source of cells with human genetic background, physiologically relevant liver functions, and unlimited supply. With over 10 years’ efforts in this field, great achievements have been made. HLCs have been successfully derived and applied in disease modeling, toxicity testing and drug discovery. Large cohorts of induced pluripotent stem cells-derived HLCs have been recently applied in studying population genetics and functional outputs of common genetic variants in vitro. This has offered a new paradigm for genome-wide association studies and possibly in vitro pharmacogenomics in the nearly future. However, HLCs have not yet been successfully applied in bioartificial liver devices and have only displayed limited success in cell transplantation. HLCs still have an immature hepatocyte phenotype and exist as a population with great heterogeneity, and HLCs derived from different hPSC lines display variable differentiation efficiency. Therefore, continuous improvement to the quality of HLCs, deeper investigation of relevant biological processes, and proper adaptation of recent advances in cell culture platforms, genome editing technology, and bioengineering systems are required before HLCs can fulfill the needs in basic and translational research. In this review, we summarize the discoveries, achievements, and challenges in the derivation and applications of HLCs.

Keywords: Hepatocyte-like cells, Human pluripotent stem cells, Hepatic differentiation, Biomedical application

Core tip: Hepatocyte-like cells (HLCs) derived from human pluripotent stem cells (hPSCs) have a great application prospect as an unlimited supply of human hepatocytes in disease modeling, toxicity testing and drug discovery. In this review, we summarize the derivation of HLCs from hPSCs, and the limitations and optimization of current differentiation protocols. We also discuss progress in the application of HLCs, and reveal the exciting future of HLCs for use in the study of rare diseases, population genetics, and in vitro pharmacogenomics.