Published online Aug 26, 2019. doi: 10.4252/wjsc.v11.i8.535
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
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.
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.