Reference : In-depth physiological characterization of primary human hepatocytes in a 3D hollow-f...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
In-depth physiological characterization of primary human hepatocytes in a 3D hollow-fiber bioreactor.
Mueller, Daniel [> >]
Tascher, Georg [> >]
Muller-Vieira, Ursula [> >]
Knobeloch, Daniel [> >]
Nuessler, Andreas K. [> >]
Zeilinger, Katrin [> >]
Heinzle, Elmar [> >]
Noor, Fozia mailto [Saarland University > Biochemical Engineering]
Journal of tissue engineering and regenerative medicine
[en] Aspartate Aminotransferases/metabolism ; Bioreactors ; Cell Culture Techniques/instrumentation/methods ; Cell Survival ; Cells, Cultured ; Cytochrome P-450 Enzyme System/metabolism ; Hepatocytes/cytology/physiology ; Humans ; Organ Specificity ; Oxygen Consumption ; Pharmaceutical Preparations/metabolism ; Substrate Specificity ; Time Factors
[en] 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 (c) 2011 John Wiley & Sons, Ltd.

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