Generation of Hepatocytes from Pluripotent Stem Cells for Drug Screening and Developmental Modeling

Methods Mol Biol. 2015;1250:123-42. doi: 10.1007/978-1-4939-2074-7_9.


Hepatocytes produced from the differentiation of human pluripotent stem cells can be used to study human development and liver disease, to investigate the toxicological response of novel drug candidates, and as an alternative source of primary cells for transplantation therapies. Here, we describe a method to produce hepatocytes by differentiating human pluripotent stem cells into definitive endoderm, patterning definitive endoderm into anterior definitive endoderm, specifying anterior definitive endoderm into hepatic endoderm, and differentiating hepatic endoderm into immature hepatocytes. These cells are further matured in either two-dimensional or three-dimensional culture conditions to produce cells capable of metabolizing xenobiotics and generating liver-specific proteins, such as albumin and alpha 1 antitrypsin.

MeSH terms

  • Cell Culture Techniques
  • Cell Differentiation / drug effects*
  • Cell Differentiation / physiology*
  • Drug Evaluation, Preclinical*
  • Endoderm / cytology
  • Endoderm / embryology
  • Hepatocytes / cytology*
  • Hepatocytes / drug effects*
  • Humans
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / drug effects*