Self‐assembled liver organoids recapitulate hepatobiliary organogenesis in vitro

Several 3D cell culture systems are currently available to create liver organoids. In general, these systems display better physiologic and metabolic aspects of intact liver tissue, compared with 2D culture systems. However, none of these reliably mimic human liver development, including parallel formation of hepatocyte and cholangiocyte anatomical structures. Here, we show that human fetal liver progenitor cells self-assemble inside acellular liver extracellular matrix (ECM) scaffolds to form 3D liver organoids that recapitulated several aspects of hepato-biliary organogenesis and resulted in concomitant formation of progressively more differentiated hepatocytes and bile duct structures. The duct morphogenesis process was interrupted by inhibiting Notch signaling, attempting to create a liver developmental disease model with a similar phenotype of Alagille syndrome. In the current study, we created an in vitro model of human liver development and disease, physiology and metabolism, supported by liver ECM substrata. We envision that it will be used in the future to study mechanisms of hepatic and biliary development, and for disease modeling and drug screening. This article is protected by copyright. All rights reserved.