Liver disease (hepatic disease) adversely affects the normal function of the liver and
causes liver problems. Drug-induced liver injury (DILI) can be predicted by primary human hepatocytes.
However, the sources of hepatocytes for large-scale drug toxicity screening are limited. To
solve this problem, pluripotent stem cells (PSCs), mesenchymal stem cells (MSCs), and hepatic
stem cells (HSCs) have emerged as attractive cell sources for cell-based therapies. Human PSCs, including
embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the ability to
undergo self-renewal and differentiate into lineages of ectoderm, mesoderm, and endoderm. Human
PSC can be used for the generation of hepatocytes to facilitate the development of novel drugs
for the treatment of severe liver diseases. The therapeutic potential of PSC-derived hepatocytes for
liver failure have been identified to enhance the development of chemically defined and xenogenic-
free 3D culture methods. To date, several hepatic differentiation strategies and various extracellular
matrix (ECM) components have been employed to produce hepatocytes or hepatic-like
cells (HLCs) in vitro. In this review, we focused on the potential of Matrigel, collagen type 1, Ro-
Gel, and laminin as ECM on the differentiation and function of hESC- and hiPSC-derived hepatocytes.
The hepatic differentiation of human ESCs and iPSCs would offer an ideal tool for cell therapy
and liver diseases.