Improved hepatocyte excretory function by immediate presentation of polarity cues

Area of Science:

• Hepatology
• Tissue Engineering
• Cell Biology

Background:

• Current in vitro hepatocyte models exhibit limited repolarization, impairing xenobiotic and waste product removal.
• Developing functional liver tissue constructs requires efficient hepatocyte excretory function for bioartificial liver devices.

Purpose of the Study:

• To investigate the impact of temporal and spatial presentation of cell matrix and cell-cell contacts on hepatocyte polarization and excretory function.
• To enhance the excretory capabilities of engineered liver tissue constructs through optimized culture conditions.

Main Methods:

• Utilized a sandwich culture configuration for spatial presentation of polarity cues.
• Introduced collagen overlay immediately upon cell-cell contact formation to improve temporal presentation of polarity cues.
• Compared outcomes with conventional 24-hour collagen overlay controls.

Main Results:

• Immediate collagen overlay enhanced apicobasolateral domain formation and tight junction development.
• Functional activity of canalicular transporters (multidrug resistance-associated protein [Mrp2] and P-glycoprotein [P-gp]) recovered significantly by 48 hours.
• Albumin secretion, urea production, and cytochrome P450 activities were enhanced over 14 days compared to controls.

Conclusions:

• Optimized temporal and spatial presentation of polarity cues, specifically immediate collagen overlay, significantly improves hepatocyte excretory function.
• Enhanced hepatocyte function in vitro may lead to improved functional maintenance and in vivo fidelity of tissue-engineered liver constructs.
• This approach holds promise for advancing bioartificial liver-assisted devices and in vivo liver modeling.