Additionally, non-parenchymal cells can also be used to better represent normal liver physiology. For example, co-cultures using hepatocytes, Kupffer cells, Stellate cells, and liver endothelial cells are already showing to be powerful tools for modeling the liver in vitro. This is because it is thought that under both normal and pathological conditions, many hepatocyte functions are regulated by substances released from neighboring non-parenchymal cells. These cells play an important role in the modulation of xenobiotic metabolism in the liver and provide more comparable data for diseased and healthy cells.
Kupffer cells are the resident macrophages in the liver and are part of the first line of defense against bacteria and toxins in the gut. Kupffer cells exhibit typical macrophage morphology and can be activated to produce inflammatory cytokines, growth factors and reactive oxygen species.
In vivo, prolonged activation of Kupffers are associated with many diseases of the liver including Non-alcoholic Fatty Liver Disease (NAFLD), Non-alcoholic Steato Hepatitis (NASH), and liver damage associated with certain bioactivated chemicals.
Kupffer cells are isolated and enriched from dissociated human liver tissue and then cryopreserved as passage 0. Characterization of isolated Kupffer cells includes assessing morphology in plated format and evaluating functional responses to LPS stimulation.
Hepatic Stellate cells are a resident cell type of the liver primarily functioning to store retinoids. In response to liver damage, Stellates rapidly lose the stored retinoids and differentiate into a proliferating fibroblast-like cell that begins depositing collagen matrix. This activity causes buildup of collagen in the liver eventually leading to cirrosis.
Stellates can be isolated from disrupted liver tissue, enriched, and placed into cell culture. Isolated and enriched Stellates are provided at passage 1, resulting in Stellates with low activation states.
Endothelial cells are the primary barrier cells that line blood vessels and sinusoids of the liver. Human Liver-derived Endothelial Cells (HLECs) provided by Lonza are isolated and enriched from disrupted liver tissue then cryopreserved for use in a wide range of research models.
HLECs express characteristic markers of endothelial cells including CD32b and vWF as shown by immunofluorescence and maintain appropriate endothelial morphology over limited serial passaging.