Table 1.

Advantages and disadvantages of using human hepatocytes or stem cell-derived hepatocyte-like cells for drug screening

Cell types	Descriptions	Advantages	Disadvantages	References
Primary human hepatocytes	Hepatocytes isolated from fresh human liver	Maintain original structure and functions, the gold standard	Limited availability, rapid dedifferentiation, and function loss	[9, 10]
Hepatic cell lines	Immortalized cell lines from human liver carcinoma cells, e.g., HepG2, Hep3B and Huh7	Easy obtainment and low cost	Loss of original characteristics of hepatocytes and inaccurate predictions	[11]
hESCs-derived HLCs	Hepatocytes differentiated from hESCs by mimicking the developmental pathway of the liver during embryogenesis	High self-renewal and pluripotency	Ethical issues	[12]
hiPSCs-derived HLCs	Hepatocytes differentiated from hiPSCs that are obtained by reprogramming of adult somatic cells	Self-renewal and pluripotency, no ethical issues, and potential to model iDILI	Low reprogramming efficiency and potential tumorigenic risk	[13, 14]
hMSCs-derived HLCs	Hepatocytes differentiated from hMSCs that can be obtained from adipose tissue, bone marrow, placenta, etc.	Abundant sources, fewer ethical concerns, and lower tumorigenic risk	Relatively low endoderm differentiation potential	[15, 16]
Transdifferentiated cells	Hepatocytes transdifferentiated directly from human adult somatic cells	Fewer operational steps	Low reprogramming efficiency, limited proliferation capacity	[17, 18]
HepaRG cells	A human bipotent progenitor cell line that can be differentiated into hepatocytes	High levels of major phase I and phase II enzymes	Low functional levels of CYP2D6, CYP2A6, and CYP2E1	[19–21]

hESCs human embryonic stem cells, HLCs hepatocyte-like cells, hiPSCs human induced pluripotent stem cells, hMSCs human mesenchymal stem cells, iDILI idiosyncratic drug-induced liver injury, CYP cytochrome P450