Survival and proliferation of liver stem/progenitor cells by liver endothelial cells
Adult liver stem/progenitor cells (LPCs) exhibit robust proliferation upon impaired hepatocyte-mediated liver regeneration. However, the regenerative capacity becomes compromised in chronic liver diseases. Consequently, the promotion of liver regeneration through the utilization of LPCs emerges as a promising alternative therapeutic strategy for patients with chronic liver diseases. LPCs can be massively expanded in vitro as self-renewing organoids, however, lack of the niche cell interactions with LPCs is a major limitation. In this study, we highlight the role of liver endothelial cells (LiECs), as a part of LPC niche cells, in supporting the hepatobiliary organoids (HOs) in long-term culture even in the absence of key growth factors, such as Wnt agonists. Furthermore, LiECs altered the gene expression profile of HOs involved in inflammation, migration, extracellular matrix organization, and receptor signaling pathway through paracrine factors. Our findings expand the role of LiECs for regulating stemness of LPCs and provide a new organoid co-culture model using reduced growth medium. Overall design: To investigate the signaling pathways in survival and proliferation of liver stem/progenitor cells by liver endothelial cells in 3D organoid culture model, we established hepatobiliary organoids co-cultured with liver endothelial cells. We isolated RNAs from hepatobiliary organoids co-cultured with or without liver endothelial cells, then perfored gene expression profiling analysis.