Immune-mediated liver injury

This really depends on the question that you want to answer. If you are interested in detecting liver-based inflammation, our standard DILI assay offering and DILI assay kit : Human 24 is sufficient. Our DILI assay contains primary human hepatocytes and Kupffer cells, which are the resident macrophage of the liver. The presence of these cells enables the model to detect inflammatory initiation in the liver.

If you want to identify drug-induced activation of the adaptive immune system and the resulting interaction with the liver, peripheral immune cells can be added into the circulating flow of the chip (e.g., peripheral blood mononuclear cells (PBMCs) or isolated immune sub-types such as T-cells). We are currently looking for partners to further validate our immune-mediated liver injury assay. Please contact us if you would like to participate.

PhysioMimix OOC technology features a closed-loop fluidic design which recirculates media around cultured microtissues, rather than single-pass fluidics. This approach facilitates concentration, rather than dilution of secreted biomarkers for easier detection. Plus, it enables the inclusion of circulating immune cells to understand their interactions with organs, the generation of an inflammatory response to stimuli or drugs, including monoclonal antibodies, and the study of inter-organ inflammatory crosstalk.

It remains a challenge to donor match all cell types due to issues sourcing all of the cell types from one donor. We have done some early work on HLA matching liver cells and peripheral immune cells, as have our customers.  The outcome of these studies suggests that it is important to HLA-match to a certain degree. A poster submitted by customers that was presented at SOT showed that, although PBMCs weren’t fully matched and some host-graft response was detected, the assay’s sensitivity was good enough to flag immune-mediated liver injury concerns found in the clinic.

All PhysioMimix Multi-chip plates (Liver-12 &-48, Barrier-12 and Dual-Organ) use circulating flow, and therefore are conducive to addition of circulating cells. Therefore, our Lung, lung/Liver and Gut/Liver models could be used for this purpose as well as the Liver. We have previously done proof-of-concept work using THP-1 monocyte cells in the Lung and Lung/Liver MPS models, whereby the monocytes were added to the circulating flow and various stimuli were used to test the inflammatory interactions between the immune cells, lung and liver microtissues. As of yet, we have not completed work in these models to test inflammatory response to compounds, however we know these models are immunocompetent and therefore will respond to inflammatory challenge.

Although these assays could potentially be useful for determining cross-species differences in drug responses, animal immune systems are very different from human and therefore recapitulating these in vitro isn’t a high priority for us at the current time.