Microfluidic Cell Culture Platforms to Capture Hepatic Physiology and Complex Cellular Interactions

Area of Science:

• Biotechnology
• Toxicology
• Drug Development

Background:

• Animal models lack human translatability for drug toxicity, leading to failures like hepatotoxicity (30% of drug failures).
• Current in vitro models (cell cultures, enzyme systems) fail to replicate human tissue complexity and dynamics.
• Preclinical species have distinct metabolic and toxicity mechanisms compared to humans.

Purpose of the Study:

• To review advancements in microtechnologies for creating physiologically relevant hepatic cell culture systems.
• To highlight microphysiological systems (MPS) as a solution to bridge the gap between animal models and conventional in vitro systems.
• To focus on MPS designed to capture in vivo physiology for improved in vitro drug testing.

Main Methods:

• Discusses microfabrication technologies for complex microfluidic systems.
• Explores methods for establishing and maintaining multicellular models that capture dynamic, human-relevant behavior.
• Highlights the design of microscale systems incorporating in vivo physiologic parameters.

Main Results:

• Microphysiological systems (MPS) show potential for generating human-relevant data for drug screening.
• MPS can better mimic organ functionality by incorporating in vivo design parameters.
• These systems aim to capture key aspects of the hepatic microenvironment for comprehensive in vitro testing.

Conclusions:

• Microphysiological systems (MPS) offer a promising approach to improve the prediction of drug-induced hepatotoxicity.
• By mimicking in vivo physiology, MPS can reduce reliance on animal testing and enhance drug safety evaluations.
• Further development in microtechnologies is advancing the creation of dynamic, human-relevant in vitro models for toxicology.