3D Cultivation Techniques for Primary Human Hepatocytes.

Bachmann A1, Moll M2, Gottwald E3, Nies C4, Zantl R5, Wagner H6, Burkhardt B7, Sánchez JJ8, Ladurner R9, Thasler W10, Damm G11, Nussler AK12.
Source: Other
Publication Date: (2015)
Issue: 4(1): 64-83
Cells used in publication:
Hepatocyte, rat
Species: rat
Tissue Origin: liver
Hepatocyte, human
Species: human
Tissue Origin: liver
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.