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Review
. 2019 Aug 26;11(8):535-547.
doi: 10.4252/wjsc.v11.i8.535.

Derivation and applications of human hepatocyte-like cells

Shuang Li  1 , Shi-Qian Huang  1 , Yong-Xu Zhao  1 , Yu-Jie Ding  2 , Dan-Jun Ma  3 , Qiu-Rong Ding  4
Affiliations
Review

Derivation and applications of human hepatocyte-like cells

Shuang Li et al. World J Stem Cells. .

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: Biomedical application; Hepatic differentiation; Hepatocyte-like cells; Human pluripotent stem cells.

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Conflict of interest statement

Conflict-of-interest statement: None of the authors have any conflicts of interest relevant to this study.

Figures

Figure 1
Figure 1
Derivation and applications of human hepatocyte-like cells. A: Directed differentiation process of human pluripotent stem cells (hPSCs)-derived hepatocyte-like cells (HLCs) in vitro includes endoderm development, endoderm hepatic specification, and hepatic maturation stages; B: Applications of human HLCs. HPSC-derived HLCs can be used to generate disease models to study rare or common genetic variants. These cellular models can be applied in pathophysiological research, drug screening, and toxicity testing. Cohorts of HLCs provide in vitro cell models for genome-wide association studies and potentially pharmacogenomics in dishes. HLCs also offer a potential cell source for bioartificial livers or liver transplantation. HLCs: Hepatocyte-like cells; hPSCs: Human pluripotent stem cells.
See this image and copyright information in PMC

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