Mouse liver assembloids model periportal architecture and biliary fibrosis.

Area of Science:

• Hepatology and Regenerative Medicine
• In Vitro Disease Modeling
• Cellular Biology

Background:

• Current in vitro liver models lack the complex cellularity and architecture of native liver tissue.
• Existing organoids fail to fully replicate in vivo liver disease progression and tissue organization.

Purpose of the Study:

• To develop a multicellular organoid system that recapitulates liver tissue architecture and models liver diseases.
• To investigate the cellular mechanisms underlying cholestatic injury and biliary fibrosis in vitro.

Main Methods:

• Generation of hepatocyte organoids with functional bile canaliculi.
• Assembly of organoids with cholangiocytes and portal fibroblasts to form liver assembloids.
• Manipulation of cell ratios and gene expression to induce disease states.

Main Results:

• Liver assembloids successfully mimic the periportal region's architecture and cellular interactions.
• The system demonstrates functional bile drainage and models cholestatic injury and biliary fibrosis.
• Fibrotic changes were induced by altering mesenchymal cell numbers, independent of immune cells.

Conclusions:

• Liver assembloids provide a robust in vitro platform for studying liver disease mechanisms.
• The model is suitable for investigating bile canaliculi formation, bile drainage, and cell-type contributions to fibrosis.
• This system facilitates research into gene function and cell-autonomous mechanisms in liver disease.