3D Primary Hepatocyte Culture Systems for Analyses of Liver Diseases, Drug Metabolism, and Toxicity: Emerging Culture Paradigms and Applications

• Published in: Biotechnology journal Vol. 14; no. 7; pp. e1800347 - n/a
• Main Authors: Lauschke, Volker M., Shafagh, Reza Z., Hendriks, Delilah F. G., Ingelman‐Sundberg, Magnus
• Format: Journal Article
• Language: English
• Published: Germany 01.07.2019
• Subjects: Cell Culture Techniques; cytochrome P450; drug metabolism; Hepatocytes - cytology; Hepatocytes - drug effects; Hepatocytes - physiology; hepatotoxicity; Humans; Lab-On-A-Chip Devices; Liver - cytology; Liver - drug effects; Liver - metabolism; Liver Diseases - metabolism; Liver Diseases - physiopathology; liver fibrosis; liver‐on‐a‐chip; microfluidic systems; Models, Biological; spheroids; Spheroids, Cellular - cytology; Spheroids, Cellular - metabolism; Spheroids, Cellular - physiology; steatosis; Toxicity Tests; liver fibrosis; hepatotoxicity; drug metabolism; liver-on-a-chip; cytochrome P450; microfluidic systems; spheroids; steatosis
• ISSN: 1860-6768; 1860-7314
• DOI: 10.1002/biot.201800347

Recent research has shown that the maintenance of relevant liver functions ex vivo requires models in which the cells exhibit an in vivo‐like phenotype, often achieved by reconstitution of appropriate cellular interactions. Multiple different models have been presented that differ in the cells utilized, media, and culture conditions. Furthermore, several technologically different approaches have been presented including bioreactors, chips, and plate‐based systems in fluidic or static media constituting of chemically diverse materials. Using such models, the ability to predict drug metabolism, drug toxicity, and liver functionality have increased tremendously as compared to conventional in vitro models in which cells are cultured as 2D monolayers. Here, the authors highlight important considerations for microphysiological systems for primary hepatocyte culture, review current culture paradigms, and discuss their opportunities for studies of drug metabolism, hepatotoxicity, liver biology, and disease. Reconstitution of liver function in vitro requires 3D culture models. Here, the authors review different materials, cells types, and methods used for good reconstitution and the applications of such systems like prediction of drug toxicity and pharmacokinetics, drug interactions, and diseased liver.