Are you still doubting whether to include immune cells in your model? Here is a reason why you should be doing it!
Drug-induced liver Injury (DILI) is an adverse drug reaction that leads to the withdrawal of drugs from the drug development process and even from the market. It burdens patients’ health, clinicians, and pharmaceutical companies.
This withdrawal highlights the need for reliable predictive preclinical models during the drug development process before they reach clinical trials and, of course, the market.
The immune system, a key player in drug toxicity testing
Although most of the drugs that generate DILI are dose-dependent and predictive, 13% of acute liver failures are considered idiosyncratic (iDILI) and independent of dose, route of administration, and duration.
Accumulating evidence indicates that most iDILI cases are mediated by immune mechanisms and interactions of these cells with parenchymal cells. Kupffer cells are specialised macrophage residents in the liver and are the key players in the hepatic immune system. Their interplay with dendritic cells, natural killer, CD4+ helper T cells, and CD8+ T cells coordinates the immune response. The extremely coordinated system, which involves diverse cascades of cytokines, suggests that immune dysregulation influences the risk of iDILI development.
The presence of both immune cells and hepatocytes is necessary to illuminate the complex crosstalk, cell interaction, and signalling that occurs in the liver during iDILI and to generate reliable screening platforms. Choosing a representative ratio of cell components in the inflammatory state is a crucial step in the co-culture design to match the hepatic physiology. To recapitulate inflammatory states, a 2.5:1 ratio of human primary hepatocytes and Kupffer cells has been used.
The inclusion of immune cells in the models ranges from 2D systems, including micropatterned cultures or transwells, to 3D approaches, Kupffer cells culture spheroids, liver organoids, or microfluidic systems to increase human primary hepatocyte functionality.
Upgrade your liver models with BeCytes
Whichever model is chosen, the inclusion of Kuppfer cells, together with others, provides an opportunity to better study iDILI while improving hepatocyte functionality.
At BeCytes, they are experts in providing primary liver cells to assist researchers in creating advanced cellular models that mimic the intricate microenvironment of the human body.
Find cryopreserved human hepatocytes and Kupffer cells in their portfolio. They also provide other non-parenchymal cells, alone or as a mix.
All their cells are isolated from healthy human liver tissue donors and undergo rigorous quality control testing to ensure optimal performance in vitro.
References
Jaeschke, H. Kupffer cells. In: J. Rodés, J.-P. Benhamou, Blei AT, Reichen J, and Rizzetto M, eds. Textbook of Hepatology: From Basic Science to Clinical Practice, 3rd ed. Iowa, USA: Blackwell Publishing Ltd; 2007: 36–42.
Reuben A, Koch DG, Lee WM. Drug-induced acute liver failure: Results of a U.S. multicenter, prospective study. Hepatology. 2010;52(6):2065-2076.
Stern S, Wang H, Sadrieh N. Microphysiological Models for Mechanistic-Based Prediction of Idiosyncratic DILI. Cells. 2023;12(11):1476.
Originally posted by BeCytes Biotechnologies on: https://becytes.com/are-you-including-kupffer-cells-in-your-hepatic-models/
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