3D Cultivation Techniques for Primary Human Hepatocytes.
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.
BG Trauma Center, Siegfried Weller Institut, Eberhard Karls University Tübingen, Schnarrenbergstr. 95, 72076 Tü̈bingen, Germany. anastasia.bachmann@gmail.com.
Anastasia
A
Bachmann
BG Trauma Center, Siegfried Weller Institut, Eberhard Karls University Tübingen, Schnarrenbergstr. 95, 72076 Tü̈bingen, Germany. matthias.moll@student.uni-tuebingen.de.
Matthias
M
Moll
Institute for Biological Interfaces, Karlsruhe Institute of Technology, POB 3640, 76021 Karlsruhe, Germany. eric.gottwald@kit.edu.
Eric
E
Gottwald
Institute for Biological Interfaces, Karlsruhe Institute of Technology, POB 3640, 76021 Karlsruhe, Germany. cordula.nies@kit.edu.
Cordula
C
Nies
GmbH, Am Klopferspitz 19, 82152 Martinsried, Germany. rzantl@ibidi.de.
Roman
R
Zantl
GmbH, Am Klopferspitz 19, 82152 Martinsried, Germany. hwagner@ibidi.de.
Helga
H
Wagner
BG Trauma Center, Siegfried Weller Institut, Eberhard Karls University Tübingen, Schnarrenbergstr. 95, 72076 Tü̈bingen, Germany. britta.burkhardt@gmx.de.
Britta
B
Burkhardt
BG Trauma Center, Siegfried Weller Institut, Eberhard Karls University Tübingen, Schnarrenbergstr. 95, 72076 Tü̈bingen, Germany. jjmartinezsanchez@live.com.
Juan J Martínez
JJ
Sánchez
Clinic for General, Visceral and Transplantation Surgery, Eberhard Karls University Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany. ruth.ladurner@med.uni-tuebingen.de.
Ruth
R
Ladurner
Department of Surgery, Ludwig-Maximilians-University of Munich Hospital Grosshadern, 81377 Munich, Germany. wolfgang.thasler@med.uni-muenchen.de.
Wolfgang
W
Thasler
Department for General, Visceral and Transplantation Surgery, Charité Medical University Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. georg.damm@charite.de.
Georg
G
Damm
BG Trauma Center, Siegfried Weller Institut, Eberhard Karls University Tübingen, Schnarrenbergstr. 95, 72076 Tü̈bingen, Germany. andreas.nuessler@gmail.com.
Andreas K
AK
Nussler
drug-induced hepatotoxicity; hydrogels; in vitro model; long-term culture; primary human hepatocytes; scaffolds; three-dimensional (3D) cell culture; two-dimensional (2D) cell culture