3D spheroid culture of hESC/hiPSC-derived hepatocyte-like cells for drug toxicity testing

Biomaterials. 2013 Feb;34(7):1781-9. doi: 10.1016/j.biomaterials.2012.11.029. Epub 2012 Dec 8.


Although it is expected that hepatocyte-like cells differentiated from human embryonic stem (ES) cells or induced pluripotent stem (iPS) cells will be utilized in drug toxicity testing, the actual applicability of hepatocyte-like cells in this context has not been well examined so far. To generate mature hepatocyte-like cells that would be applicable for drug toxicity testing, we established a hepatocyte differentiation method that employs not only stage-specific transient overexpression of hepatocyte-related transcription factors but also a three-dimensional spheroid culture system using a Nanopillar Plate. We succeeded in establishing protocol that could generate more matured hepatocyte-like cells than our previous protocol. In addition, our hepatocyte-like cells could sensitively predict drug-induced hepatotoxicity, including reactive metabolite-mediated toxicity. In conclusion, our hepatocyte-like cells differentiated from human ES cells or iPS cells have potential to be applied in drug toxicity testing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cells, Cultured
  • Embryonic Stem Cells / cytology*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Hepatocytes / drug effects*
  • Humans
  • Immunohistochemistry
  • Pluripotent Stem Cells / cytology*
  • Toxicity Tests / methods*