Co-culture with non-parenchymal cells
Many pathological events that form the basis of various liver diseases, such as hepatitis or fibrosis, or constitute adverse events due to drugs, manifest as a result of an interaction between hepatocytes and other non-parenchymal cells (NPCs). Thus, a predictive in vitro system should be able to emulate these cross-cell type interactions.
The 3D spheroid system supports the long-term co-culture with NPCs that are present in human liver in vivo, such as Kupffer, stellate and biliary cells, thus mimicking the whole cellular repertoire of human liver cells, thus supporting the in vitro replication of complex ADRs and hepatic diseases (Fig. 1).
Figure 1: The 3D spheroid culture supports co-culture with non-parenchymal Kupffer, stellate and biliary cells. Immunofluorescent stainings (a) reveal the presence of non-parenchymal cells (NPC), such as Kupffer cells, stellate cells and biliary cells in co-cultured spheroids even after multiple weeks in culture. b, Co-cultured Kupffer cells were responsive to LPS-mediated activation as evidenced by elevated IL-6 secretion. n= 3. Error bars indicate s.d. All scale bars = 100 µm. Figure modified from Bell et al., Sci Rep, 2016.