3D Cultivation Techniques for Primary Human Hepatocytes

Microarrays

Anastasia Bachmann¹  Matthias Moll¹  Eric Gottwald⁴  Cordula Nies⁴  Roman Zantl²  Helga Wagner²  Britta Burkhardt¹  Juan J. Martínez Sánchez¹  Ruth Ladurner⁷  Wolfgang Thasler⁶  Georg Damm³  Andreas K. Nussler¹  Mohammad Reza Lornejad-Schr⁵ 

[1] BG Trauma Center, Siegfried Weller Institut, Eberhard Karls University Tübingen, Schnarrenbergstr. 95, 72076 Tü̈bingen, Germany; E-Mails:;ibidi GmbH, Am Klopferspitz 19, 82152 Martinsried, Germany; E-Mails:;Department for General, Visceral and Transplantation Surgery, Charité Medical University Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; E-Mail:;Institute for Biological Interfaces, Karlsruhe Institute of Technology, POB 3640, 76021 Karlsruhe, Germany; E-Mails:BG Trauma Center, Siegfried Weller Institut, Eberhard Karls University Tübingen, Schnarrenbergstr. 95, 72076 Tü̈bingen, Germany;;Department of Surgery, Ludwig-Maximilians-University of Munich Hospital Grosshadern, 81377  Munich, Germany; E-Mail:;Clinic for General, Visceral and Transplantation Surgery, Eberhard Karls University Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany; E-Mail:

关键词: primary human hepatocytes;    three-dimensional (3D) cell culture;    two-dimensional (2D) cell culture;    in vitro model;    hydrogels;    scaffolds;    drug-induced hepatotoxicity;    long-term culture;   

DOI  :  10.3390/microarrays4010064

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.