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Table 1 Advantages and disadvantages of using human hepatocytes or stem cell-derived hepatocyte-like cells for drug screening

From: Advancements in stem cell-derived hepatocyte-like cell models for hepatotoxicity testing

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

[19,20,21]

  1. 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