Multi-cell type human liver microtissues for hepatotoxicity testing

Arch Toxicol. 2013 Jan;87(1):209-13. doi: 10.1007/s00204-012-0968-2. Epub 2012 Nov 11.


Current 2-dimensional hepatic model systems often fail to predict chemically induced hepatotoxicity due to the loss of a hepatocyte-specific phenotype in culture. For more predictive in vitro models, hepatocytes have to be maintained in a 3-dimensional environment that allows for polarization and cell-cell contacts. Preferably, the model will reflect an in vivo-like multi-cell type environment necessary for liver-like responses. Here, we report the characterization of a multi-cell type microtissue model, generated from primary human hepatocytes and liver-derived non-parenchymal cells. Liver microtissues were stable and functional for 5 weeks in culture enabling, for example, long-term toxicity testing of acetaminophen and diclofenac. In addition, Kupffer cells were responsive to inflammatory stimuli such as LPS demonstrating the possibility to detect inflammation-mediated toxicity as exemplified by the drug trovafloxacin. Herewith, we present a novel 3D liver model for routine testing in 96-well format capable of reducing the risk of unwanted toxic effects in the clinic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fluoroquinolones / toxicity
  • Hepatocytes / cytology*
  • Hepatocytes / drug effects*
  • Humans
  • Kupffer Cells / drug effects
  • Lipopolysaccharides / pharmacology
  • Naphthyridines / toxicity
  • Tissue Culture Techniques
  • Toxicity Tests / methods*


  • Fluoroquinolones
  • Lipopolysaccharides
  • Naphthyridines
  • trovafloxacin