In-depth physiological characterization of primary human hepatocytes in a 3D hollow-fiber bioreactor†
Daniel Mueller
Biochemical Engineering Institute, Campus A1 5, Saarland University, D-66123 Saarbruecken, Germany
Search for more papers by this authorGeorg Tascher
Biochemical Engineering Institute, Campus A1 5, Saarland University, D-66123 Saarbruecken, Germany
Search for more papers by this authorUrsula Müller-Vieira
Pharmacelsus GmbH, Science Park 2, D-66123 Saarbruecken, Germany
Search for more papers by this authorDaniel Knobeloch
Department of General, Visceral and Transplantation Surgery, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, D-13353 Berlin, Germany
Search for more papers by this authorAndreas K. Nuessler
Department. of Traumatology, TU Munich, MRI, Ismaningerstrasse 22, D-81675 Munich, Germany
Search for more papers by this authorKatrin Zeilinger
Bioreactor group, Division of Experimental Surgery, Berlin Brandenburg Centre for Regenerative Therapies (BCRT), Charité Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany
Search for more papers by this authorElmar Heinzle
Biochemical Engineering Institute, Campus A1 5, Saarland University, D-66123 Saarbruecken, Germany
Search for more papers by this authorCorresponding Author
Fozia Noor
Biochemical Engineering Institute, Campus A1 5, Saarland University, D-66123 Saarbruecken, Germany
Biochemical Engineering Institute, Saarland University, Campus A1 5, D-66123 Saarbruecken, Germany.Search for more papers by this authorDaniel Mueller
Biochemical Engineering Institute, Campus A1 5, Saarland University, D-66123 Saarbruecken, Germany
Search for more papers by this authorGeorg Tascher
Biochemical Engineering Institute, Campus A1 5, Saarland University, D-66123 Saarbruecken, Germany
Search for more papers by this authorUrsula Müller-Vieira
Pharmacelsus GmbH, Science Park 2, D-66123 Saarbruecken, Germany
Search for more papers by this authorDaniel Knobeloch
Department of General, Visceral and Transplantation Surgery, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, D-13353 Berlin, Germany
Search for more papers by this authorAndreas K. Nuessler
Department. of Traumatology, TU Munich, MRI, Ismaningerstrasse 22, D-81675 Munich, Germany
Search for more papers by this authorKatrin Zeilinger
Bioreactor group, Division of Experimental Surgery, Berlin Brandenburg Centre for Regenerative Therapies (BCRT), Charité Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany
Search for more papers by this authorElmar Heinzle
Biochemical Engineering Institute, Campus A1 5, Saarland University, D-66123 Saarbruecken, Germany
Search for more papers by this authorCorresponding Author
Fozia Noor
Biochemical Engineering Institute, Campus A1 5, Saarland University, D-66123 Saarbruecken, Germany
Biochemical Engineering Institute, Saarland University, Campus A1 5, D-66123 Saarbruecken, Germany.Search for more papers by this authorThis 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.
Abstract
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.
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