It’s just the size of a droplet, but it functions like the real thing. A new organoid model replicates the liver’s most complex region—offering a powerful tool to fight liver disease and test new drugs.
Key Points at a Glance
- Dresden scientists developed the first liver organoid with three core liver cell types
- The model mimics real liver bile flow and can replicate cholestatic injury and fibrosis
- It enables disease modeling and testing gene function in a physiologically relevant way
- Could revolutionize drug screening and liver disease research using human cells
In a major leap for organoid research, scientists at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden have created a tiny but functional replica of one of the liver’s most intricate regions—the periportal zone. This new model, called a “periportal assembloid,” features three types of liver cells, assembles like biological LEGO, and drains bile just like a real liver.
Published in the journal Nature, the study describes how researchers combined hepatocytes, cholangiocytes, and liver fibroblasts into a single 3D structure that mimics the liver’s bile-draining canal system. It marks the first time these critical cell types have been successfully integrated into one organoid platform.
“Our assembloid reconstructs the liver periportal region and can model aspects of cholestatic liver injury and biliary fibrosis,” said postdoc and co-first author Anna Dowbaj, soon to join the Technical University of Munich. “This region is key because when bile drainage is disrupted, it’s where damage and disease often begin.”
Hepatocytes are the liver’s functional workhorses. In this new model, they form bile canaliculi—microscopic channels that drain bile into the ductal system. By adding cholangiocytes (which line bile ducts) and fibroblasts (which contribute to scarring), the team recreated the micro-architecture of the periportal area with remarkable precision.
“The liver model works like real liver tissue, moving bile from inside liver cells into bile ducts,” explained Aleksandra Sljukic, a doctoral student and co-author. “It shows we can replicate the cell interactions critical to liver function.”
The team went further, showing that by manipulating the number of mesenchymal cells, they could induce fibrosis-like changes—providing a new platform for understanding scarring in liver disease. They also demonstrated how gene mutations can be introduced to study their role in disease onset and progression.
Heather Harrington and her colleagues at the University of Oxford used topological data analysis to reveal that specific assembloid shapes correlate with stronger liver functionality, offering a way to quantify and predict organoid performance over time.
Senior author and MPI-CBG director Meritxell Huch emphasized the breakthrough’s modular power. “Although we’re still missing endothelial and immune cells, this is the first time we’ve built a model that captures the periportal liver structure so precisely,” she said. “It’s easy to manipulate, and we believe it will become a foundational tool for liver research.”
Looking forward, the researchers plan to adapt the model for use with human cells. If successful, it could transform pharmaceutical screening by offering a more realistic 3D platform for studying drug toxicity and disease mechanisms—far beyond what flat 2D cell cultures can offer.
In essence, this assembloid isn’t just a model of the liver. It’s a model for the future of biomedical research: modular, functional, and astonishingly lifelike.
Source: Max Planck Institute CBG
