Liver organoid and assembloid models are promising tools for studying human liver development and disease, but mostly rely on pluripotent stem cells that only partially recapitulate the cellular complexity of native liver tissue. Writing in Nature, Yuan et al. develop a human periportal liver assembloid model using primary cells derived from adult donors, recapitulating the three main cell types essential for liver function: hepatocytes, mesenchymal cells and cholangiocytes (epithelial cells of the bile duct).
The authors analyzed signaling pathways involved in hepatocyte proliferation, identifying a combination of WNT and YAP activation that enabled the long-term expansion of human adult hepatocytes as organoids. They obtained human hepatocyte organoids from samples taken from 28 patients. Upon maturation, hepatocyte organoids resembled in vivo tissue, including showing apical–basal cell polarity, and recapitulated patient-specific variability in bile canaliculus morphology and metabolic profiles.
