Probing heterotypic cell interactions: hepatocyte function in microfabricated co-cultures

Area of Science:

• Biomedical Engineering
• Cell Biology
• Hepatology

Background:

• Bioartificial liver devices aim to replace liver function but face challenges due to the instability of isolated hepatocytes in vitro.
• Co-culturing hepatocytes with mesenchymal cells can stabilize liver-specific functions, but this approach has not been successfully integrated into bioreactor systems.

Purpose of the Study:

• To investigate the role of heterotypic cell interactions in inducing and stabilizing liver-specific functions.
• To understand the cellular microenvironment required for maintaining hepatocyte function.
• To inform the design of co-culture based bioartificial liver systems.

Main Methods:

• Utilized microfabrication and conventional techniques to control the interface between hepatocytes and 3T3 fibroblasts.
• Examined the effects of varying degrees of heterotypic interaction on liver tissue function, specifically albumin and urea synthesis.
• Compared hepatic functions in hepatocytes near and far from the fibroblast interface.

Main Results:

• Maximal induction of liver-specific functions was observed in co-cultures with the highest degree of initial heterotypic interaction.
• Hepatocytes in close proximity to fibroblasts exhibited enhanced hepatic functions compared to those further away.
• Data suggested that direct heterotypic cell contact is essential for the induction of these functions.

Conclusions:

• Heterotypic cell interactions, particularly direct contact, are critical for inducing and stabilizing hepatocyte functions.
• These findings provide essential design criteria for developing functional co-culture based bioartificial liver devices.
• The study offers a valuable model for investigating the impact of cell-cell interactions on liver physiology and pathophysiology.