Applications and limitations of pluripotent stem cell-derived liver organoids

Liver disease is one of leading causes of death worldwide. However, current liver models have limited research progress. Therefore, models that accurately reflect the physiological functions of the human liver are urgently needed in both clinical and laboratory research. Over the past decade, liver organoids have emerged as valuable research tools offering significant breakthroughs and demonstrating great promise as advanced liver models. Liver organoids derived from pluripotent stem cells (PSCs), including embryonic and induced pluripotent stem cells, have shown significant potential for modeling liver diseases and drug responses. These miniature three-dimensional (3D) structures replicate the complexity of the liver and offer a platform for studying liver development and disease progression. The ability to create personalized organoids from patient-derived cells paves the way for precision medicine and drug screening. Owing to the pluripotency of PSCs, PSC-derived liver organoids (PSC-LOs) closely mimic the true structure of the liver and offer a wide range of applications. With advances in research, bioengineered liver organoids have the potential to revolutionize regenerative medicine, disease modeling, and the understanding of liver pathophysiology. This review provides an overview of liver organoid development and discusses their applications in liver regeneration, disease modeling, drug screening, toxicity assessment, organ transplantation, and regenerative medicine. Finally, we discuss the limitations and future development directions of PSC-LOs.