Gradient-Based Regulation of Activin A Directs Multilineage Liver Organoid Development from Human Pluripotent Stem Cells

This publication describes a scalable approach for generating multilineage liver organoids from human pluripotent stem cells using a PBS Mini Vertical-Wheel bioreactor. The authors examined how different Activin A concentrations influence endoderm and mesenchymal lineage emergence during liver organoid formation. High Activin A concentrations promoted homogeneous definitive endoderm induction and enhanced hepatic maturation markers, whereas lower concentrations generated morphologies resembling early liver diverticula with lumen-like structures, hepatic mesenchymal populations, endothelial markers, and extracellular matrix organization. Transcriptomic, immunohistochemical, and developmental analyses demonstrated coordinated formation of hepatic and non-parenchymal cell populations that recapitulate features of early liver bud morphogenesis. The study presents a scalable organoid platform for investigating liver development, morphogen-driven tissue patterning, disease modeling, and future regenerative medicine applications.