Will we ever model PSC? - "it's hard to be a PSC model!".

Area of Science:

• Hepatology and Gastroenterology
• Immunology and Pathology

Background:

• Cholangiopathies, like primary sclerosing cholangitis (PSC), are serious liver diseases affecting bile ducts, leading to significant illness and death.
• Limited treatment options and challenges in studying the human bile duct system hinder understanding of PSC pathophysiology.
• There is a critical need for reproducible animal models to study PSC and evaluate new therapies.

Purpose of the Study:

• To systematically review and critically analyze existing rodent models for sclerosing cholangitis and biliary fibrosis.
• To assess the suitability of current models for investigating PSC pathophysiology and testing therapeutic interventions.

Main Methods:

• Comprehensive literature review of rodent models.
• Analysis of models including chemically-induced cholangitis, knockout mice, infectious agents, biliary obstruction, and gut-related models.
• Evaluation of models based on reproducibility and relevance to PSC.

Main Results:

• Various rodent models exist for studying cholangitis and biliary fibrosis, including chemically-induced, genetic, infectious, obstructive, and gut-associated models.
• No single current model perfectly replicates all aspects of human PSC, particularly the combination of intra- and extrahepatic biliary fibrosis with colitis.
• Each model type offers unique insights but has limitations in fully recapitulating the complex pathophysiology of PSC.

Conclusions:

• Current rodent models provide valuable tools for dissecting specific aspects of sclerosing cholangitis and biliary fibrosis.
• Further development is needed to create more comprehensive and reproducible models that mimic human PSC more closely.
• Improved animal models are essential for advancing research into PSC and developing effective treatments.