Liver Reconstruction Model | Complex Architecture
- Researchers have developed a next-generation liver organoid model, called a "periportal assembloid," to better understand liver diseases.
- The assembloid effectively drains bile from bile canaliculi into the bile duct, mirroring the function of a real liver.Anna Dowbaj, a postdoctoral researcher in the Huch group, noted...
- The team, including Aleksandra Sljukic, a doctoral student, assembled the model in steps, first creating hepatocyte organoids with working bile channels.
Advanced Liver Models Offer insights into Cholestatic Liver Injury
Researchers have developed a next-generation liver organoid model, called a “periportal assembloid,” to better understand liver diseases. This new model, created by Meritxell Huch’s team at the Max Planck Institute of Molecular Cell Biology and Genetics, includes adult hepatocytes, cholangiocytes, and liver mesenchymal cells, reconstructing the liver’s periportal region.
The assembloid effectively drains bile from bile canaliculi into the bile duct, mirroring the function of a real liver.Anna Dowbaj, a postdoctoral researcher in the Huch group, noted that this model can simulate aspects of cholestatic liver injury and biliary fibrosis. The periportal region, crucial for bile transport, is often disrupted in liver diseases.
The team, including Aleksandra Sljukic, a doctoral student, assembled the model in steps, first creating hepatocyte organoids with working bile channels. They then added cholangiocytes and fibroblast cells. By manipulating mesenchymal cell numbers, they induced a response similar to liver fibrosis and demonstrated the model’s utility in studying gene roles in liver disease.
Heather Harrington’s team at the University of Oxford used topological data analysis to classify assembloid shapes, finding correlations between certain shapes and improved liver function.
“Our assembloid reconstructs the liver periportal region and can model aspects of cholestatic liver injury and biliary fibrosis,” Anna Dowbaj said.
Huch envisions using thes periportal liver models to study disease mechanisms and, eventually, to conduct more physiologically relevant drug efficacy and toxicity studies using human cells.
What’s next
Future research will focus on incorporating endothelium and immune cells into the model to create an even more comprehensive representation of the liver, potentially leading to more effective treatments for liver diseases.