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The Multi-organ Chip - A Microfluidic Platform for Long-term Multi-tissue Coculture
Published on: April 28, 2015
A microfluidic hepatic coculture platform for cell-based drug metabolism studies
Eric Novik1, Timothy J Maguire, Piyun Chao
1Hurel Corporation, Beverley Hills, California, CA, USA.
Biochemical Pharmacology
|November 21, 2009
Summary
This study introduces a novel microfluidic platform using hepatic coculture for more accurate in vitro drug screening. The system enhances prediction of human physiological responses and metabolite generation, reducing late-stage trial failures.
Area of Science:
- Pharmacology
- Biotechnology
- In vitro toxicology
Background:
- Current in vitro drug screening methods, like suspended human hepatocytes, lack long-term cellular function, limiting their predictive value for human in vivo responses.
- There is a critical need for more human-relevant in vitro systems in the pharmaceutical and biotech industries to reduce costly clinical trial failures and animal testing.
- Improving the predictability of in vitro assays is essential for efficient drug development and safety assessment.
Purpose of the Study:
- To establish and evaluate an integrated, microfluidic, in vitro platform combining a microdevice with a hepatic coculture system.
- To assess the platform's utility in studying compound clearance and metabolite generation.
- To demonstrate the enhanced predictive value and resolution of this flow-based coculture system compared to static methods.
Main Methods:
- Development of an integrated microfluidic platform incorporating the HmuREL((R)) microdevice and a hepatic coculture system.
- Utilizing the platform to study the clearance and metabolite generation of various molecular entities under flow conditions.
- Comparison of results obtained from the flow-based coculture system with traditional static culture systems.
Main Results:
- The flow-based hepatic coculture system demonstrated improved resolution and predictive value in clearing compounds across high, medium, and low clearance ranges.
- Coupling coculture with flow conditions resulted in significantly higher metabolite production rates compared to static systems.
- The platform successfully maintained cellular function over time, addressing a key limitation of current in vitro models.
Conclusions:
- The integrated microfluidic hepatic coculture platform offers a more human-relevant in vitro screening system for drug development.
- This advanced system enhances the prediction of in vivo physiological responses, aiding in the reduction of late-stage pharmaceutical failures.
- The platform provides a valuable tool for studying drug metabolism and clearance, potentially reducing the need for animal testing.
