A Bile Duct-on-a-Chip With Organ-Level Functions

Area of Science:

• * Organ-on-a-chip technology
• * Biliary epithelial biology
• * Hepatology

Background:

• * Chronic cholestatic liver diseases, including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), often involve impaired biliary epithelial barrier function.
• * Current in vitro models do not fully recapitulate the complex 3D architecture and functional barrier properties of native bile ducts.

Purpose of the Study:

• * To develop and validate a bile duct-on-a-chip model that mimics the structural and functional characteristics of the native bile duct.
• * To utilize this platform for studying bile duct pathophysiology and evaluating the toxicity of biliary compounds.

Main Methods:

• * Engineered a microfluidic device to culture primary mouse cholangiocytes in a 3D tubular architecture.
• * Assessed cholangiocyte polarization, tight junction formation, and monolayer permeability.
• * Investigated mechanosensitivity and performed toxicity studies using biliatresone and glycochenodeoxycholic acid.

Main Results:

• * The bile duct-on-a-chip successfully replicated bile duct tubular architecture and barrier functions.
• * Cholangiocytes formed polarized monolayers with mature tight junctions and exhibited mechanosensitive responses.
• * The basolateral surface was more susceptible to toxicity than the apical surface, highlighting the protective role of the apical glycocalyx.

Conclusions:

• * The bile duct-on-a-chip serves as a functional in vitro platform for studying bile duct physiology and disease.
• * This model enables investigation of cholangiocyte responses to toxins and mechanical stimuli.
• * It provides insights into the protective mechanisms of the biliary epithelium in chronic liver diseases.