In-depth physiological characterization of primary human hepatocytes in a 3D hollow-fiber bioreactor

Daniel Mueller, Georg Tascher, Ursula Müller-Vieira, Daniel Knobeloch, Andreas K. Nuessler, Katrin Zeilinger, Elmar Heinzle, Fozia Noor*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

39 Citations (Scopus)


As the major research focus is shifting to three-dimensional (3D) cultivation techniques, hollow-fiber bioreactors, allowing the formation of tissue-like structures, show immense potential as they permit controlled in vitro cultivation while supporting the in vivo environment. In this study we carried out a systematic and detailed physiological characterization of human liver cells in a 3D hollow-fiber bioreactor system continuously run for > 2 weeks. Primary human hepatocytes were maintained viable and functional over the whole period of cultivation. Both general cellular functions, e.g. oxygen uptake, amino acid metabolism and substrate consumption, and liver-specific functions, such as drug-metabolizing capacities and the production of liver-specific metabolites were found to be stable for > 2 weeks. As expected, donor-to-donor variability was observed in liver-specific functions, namely urea and albumin production. Moreover, we show the maintenance of primary human hepatocytes in serum-free conditions in this set-up. The stable basal cytochrome P450 activity 3 weeks after isolation of the cells demonstrates the potential of such a system for pharmacological applications. Liver cells in the presented 3D bioreactor system could eventually be used not only for long-term metabolic and toxicity studies but also for chronic repeated dose toxicity assessment.

Original languageEnglish
Pages (from-to)e207-e218
JournalJournal of Tissue Engineering and Regenerative Medicine
Issue number8
Publication statusPublished - Aug 2011
Externally publishedYes


  • 3D cultivation
  • Cell metabolism
  • CYP 450
  • Liver
  • Long-term studies
  • Metabolic activity
  • Toxicity


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