In the next steps of this work, HZI and InSCREENeX will increase the number of available cell lines to cover various species (mice, rats, pigs, cows, humans) and cell types (endothelial cells, fibroblasts, lung epithelial cells, hepatocytes, chondrocytes).
A similar approach has been taken by Medicyte, which tranduces proliferation-stimulating genes into primary human hepatocytes to create longer-living cells dubbed upcyte® hepatocytes. These cells are then grown in 3D cultures by seeding them onto alvetex scaffolds. Recent work has focused on the 3D cultures’ drug-metabolizing activity and application to cytotoxicity and drug interaction assays.
Compared to 2D monolayer cultures, the 3D cultures seem to demonstrate enhanced CYP1A2, CYP2B6, and CYP3A4 enzyme activities, both at baseline levels and when induced by drugs such as omeprazole, phenobarbitone, and rifampin, respectively.
Nicola Hewitt, Ph.D., a scientific consultant at Medicyte, is enthusiastic about the new opportunities made possible by 3D hepatocyte cultures.
“We are investigating the use of upcyte hepatocytes in bioartificial liver (BAL) models as part of two European projects (HemiBio and ReLiver),” said Dr. Hewitt. “In these projects, other ‘upcyted’ cells such as endothelial and stellate cells will be co-cultured with hepatocytes to form a much more in vivo-like culture structure. This gives us the possibility to extend this work to therapeutic areas.”
In addition, said Dr. Hewitt, “We are also looking into whether the 3D culture of hepatocytes—with and without co-culturing with other cell types—can result in a model that is more predictive than previous hepatotoxicity prediction models, which may be based on the less relevant hepatoblastoma cell line, HepG2. If we can produce a model that can pick up the hepatotoxicity of drugs that have been withdrawn from the market due to liver toxicity, then this would be a powerful tool to prevent such compounds reaching the market.”