Construction of liver organoid models by hepatobiliary differentiation from human induced pluripotent stem cells: state of the art, challenges and improving strategies

• Liver organoids derived from iPSCs hold promise for disease modeling and drug development, but face bottlenecks such as incomplete maturation and lack of non-parenchymal cells. • The review emphasizes multidimensional regulation of hepatobiliary development, including cellular origin, culture system, and microenvironment, to improve differentiation outcomes. • Future directions include elucidating self-assembly mechanisms, using small-molecule compounds to standardize protocols, advancing transplantation for functional validation, and integrating AI for precise regulation. • Standardized differentiation protocols and incorporation of immune and stromal cells are critical for enhancing the physiological relevance of liver organoids.