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From the third issue of 2017, Microarrays has changed its name to High-Throughput.

Open AccessReview

3D Cultivation Techniques for Primary Human Hepatocytes

BG Trauma Center, Siegfried Weller Institut, Eberhard Karls University Tübingen, Schnarrenbergstr. 95, 72076 Tü̈bingen, Germany
Institute for Biological Interfaces, Karlsruhe Institute of Technology, POB 3640, 76021 Karlsruhe, Germany
GmbH, Am Klopferspitz 19, 82152 Martinsried, Germany
Clinic for General, Visceral and Transplantation Surgery, Eberhard Karls University Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany
Department of Surgery, Ludwig-Maximilians-University of Munich Hospital Grosshadern, 81377 Munich, Germany
Department for General, Visceral and Transplantation Surgery, Charité Medical University Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
Author to whom correspondence should be addressed.
Academic Editors: Mohammad Reza Lornejad-Schäfer and Christine Schäfer
Microarrays 2015, 4(1), 64-83;
Received: 15 December 2014 / Revised: 8 January 2015 / Accepted: 3 February 2015 / Published: 16 February 2015
(This article belongs to the Special Issue Advantages of Three Dimensional (3D) Cell Cultures)
PDF [886 KB, uploaded 17 February 2015]


One of the main challenges in drug development is the prediction of in vivo toxicity based on in vitro data. The standard cultivation system for primary human hepatocytes is based on monolayer cultures, even if it is known that these conditions result in a loss of hepatocyte morphology and of liver-specific functions, such as drug-metabolizing enzymes and transporters. As it has been demonstrated that hepatocytes embedded between two sheets of collagen maintain their function, various hydrogels and scaffolds for the 3D cultivation of hepatocytes have been developed. To further improve or maintain hepatic functions, 3D cultivation has been combined with perfusion. In this manuscript, we discuss the benefits and drawbacks of different 3D microfluidic devices. For most systems that are currently available, the main issues are the requirement of large cell numbers, the low throughput, and expensive equipment, which render these devices unattractive for research and the drug-developing industry. A higher acceptance of these devices could be achieved by their simplification and their compatibility with high-throughput, as both aspects are of major importance for a user-friendly device. View Full-Text
Keywords: primary human hepatocytes; three-dimensional (3D) cell culture; two-dimensional (2D) cell culture; in vitro model; hydrogels; scaffolds; drug-induced hepatotoxicity; long-term culture primary human hepatocytes; three-dimensional (3D) cell culture; two-dimensional (2D) cell culture; in vitro model; hydrogels; scaffolds; drug-induced hepatotoxicity; long-term culture

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Bachmann, A.; Moll, M.; Gottwald, E.; Nies, C.; Zantl, R.; Wagner, H.; Burkhardt, B.; Sánchez, J.J.M.; Ladurner, R.; Thasler, W.; Damm, G.; Nussler, A.K. 3D Cultivation Techniques for Primary Human Hepatocytes. Microarrays 2015, 4, 64-83.

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