Professor Yohan Kim of the Department of MetaBioHealth at Sungkyunkwan University (President Yoo Ji-Beom), in collaboration with the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Germany, has successfully developed human periportal liver assembloids that precisely reproduce the periportal region of the human liver outside the body. This achievement was recognized for its scientific significance and published on December 17, 2025 in Nature, the world's most prestigious journal in life sciences.

The liver-often referred to as the body's "chemical factory"-is responsible for essential functions such as metabolism, detoxification, and bile production. Until now, researchers have relied on organoids-miniature organ-like structures grown from stem cells-to study liver disease in the laboratory. However, conventional liver organoids have been limited in their ability to reproduce the complex interactions among diverse liver cell types, making it difficult to reflect the liver's highly sophisticated architecture and function in the human body.

To overcome these limitations, Professor Kim utilized patient-derived liver tissue obtained during surgery. The researchers established a technology that enables the direct expansion of mature human hepatocytes in vitro and successfully generated hepatocyte organoids. These organoids formed functional bile canaliculi, retained long-term metabolic activity, and demonstrated drug detoxification and energy metabolism comparable to the human liver.

Taking the approach further, the team combined hepatocyte organoids with bile duct organoids and periportal fibroblasts derived from the same patient. By assembling these components in a highly controlled three-dimensional architecture-much like building with LEGO blocks-they created periportal liver assembloids. The term assembloid refers to a next-generation engineered tissue constructed by assembling multiple cell types or organoids into a unified functional structure.

The resulting assembloids faithfully reproduced the periportal region of the human liver, where hepatocytes, bile ducts, and blood vessels converge and active molecular exchange occurs. Transcriptomic analysis revealed that the assembloids carried out complex liver-specific functions such as gluconeogenesis and urea metabolism. Notably, the team also demonstrated hepatic zonation, in which cells adopt different functional identities depending on their spatial location-one of the most defining features of the native liver.

This breakthrough has profound implications for reducing animal experimentation and accelerating patient-specific therapies. By artificially increasing fibroblast populations within the assembloids, the team generated a liver fibrosis model, in which pathological features such as collagen deposition and cell death observed in cirrhotic patients could be faithfully reproduced and studied in vitro.

Professor Kim stated, "This is the world's first demonstration that multiple patient-derived liver cell types can be assembled into a single functional tissue that recapitulates the structural and pathological complexity of the human liver in the laboratory. Going forward, this platform will enable the development of new treatments for liver fibrosis, biliary diseases, and liver cancer, and will allow patient-specific drug testing as a precision medicine tool."

This study was supported by the Max Planck Society, the German Federal Ministry of Education and Research (BMBF), and the European Research Council (ERC).

※ Title: Human assembloids recapitulate periportal liver tissue in vitro

※ Journal: Nature (Published on 17th of December, 2025)

※ DOI: https://www.nature.com/articles/s41586-025-09884-1

※ Pure: https://pure.skku.edu/en/persons/yohan-kim/

▲Schematic of human hepatocyte-derived organoid generation and periportal liver assembloid