Liver-specific functional studies in a microfluidic array of primary mammalian hepatocytes

Area of Science:

• Hepatocyte research
• Microfluidics
• Toxicology

Background:

• Drug development faces significant financial losses due to liver toxicity failures.
• Hepatocyte-based systems can model liver responses to toxic insults, potentially reducing late-stage failures.
• Current methods lack the throughput for comprehensive liver toxicity assessment.

Purpose of the Study:

• To develop a microfluidic array of primary hepatocytes for high-throughput liver toxicity studies.
• To create a system capable of modeling in vivo liver tissue response to toxic insults.
• To advance drug development by providing a more accurate preclinical toxicity screening tool.

Main Methods:

• Fabrication of a 64-element microfluidic well array.
• Co-culturing micropatterned primary rat hepatocytes with 3T3-J2 fibroblasts.
• Utilizing dual microfluidic perfusion networks for continuous medium and oxygen supply.
• Developing selective patterning techniques for hepatocytes and fibroblasts.

Main Results:

• Demonstrated continuous, steady-state albumin synthesis (78.4 μg/day).
• Showcased consistent urea production (109.8 μg/day).
• Validated the array's capacity for sustained metabolic and synthetic function.

Conclusions:

• The developed microfluidic hepatocyte array shows promise for physiologically relevant toxicology studies.
• This system can contribute to reducing drug developmental failures caused by liver toxicity.
• Further development aims to enhance the array for comprehensive preclinical safety assessments.