An extracellular matrix-based culture system for generation of human pluripotent stem cell derived-hepatocytes.

Liver disease (hepatic disease) adversely affects the normal function of the liver and causes liver problems. Druginduced liver injury (DILI) can be predicted by primary human hepatocytes. However, the sources of hepatocytes for largescale 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 to differentiate into lineages of ectoderm, mesoderm, and endoderm. Human PSC can be used for generation of hepatocytes to facilitate the development of novel drugs for 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, RoGel, 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.