This article was published online on 27 March 2011. An error was subsequently identified in the legend of figure 5b. This notice is included in the online and print versions to indicate that both have been corrected on 17 June 2011.
In-depth physiological characterization of primary human hepatocytes in a 3D hollow-fiber bioreactor†
Article first published online: 27 MAR 2011
Copyright © 2011 John Wiley & Sons, Ltd.
Journal of Tissue Engineering and Regenerative Medicine
Volume 5, Issue 8, pages e207–e218, August 2011
How to Cite
Mueller, D., Tascher, G., Müller-Vieira, U., Knobeloch, D., Nuessler, A. K., Zeilinger, K., Heinzle, E. and Noor, F. (2011), In-depth physiological characterization of primary human hepatocytes in a 3D hollow-fiber bioreactor. J Tissue Eng Regen Med, 5: e207–e218. doi: 10.1002/term.418
- Issue published online: 20 JUL 2011
- Article first published online: 27 MAR 2011
- Manuscript Accepted: 21 FEB 2011
- Manuscript Received: 2 SEP 2010
- German BMBF
- metabolic activity;
- CYP 450;
- cell metabolism;
- long-term studies;
- 3D cultivation;
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. Copyright © 2011 John Wiley & Sons, Ltd.