Thyroid-on-a-Chip: An Organoid Platform for In Vitro Assessment of Endocrine Disruption

Area of Science:

• Endocrinology
• Toxicology
• Biomedical Engineering

Background:

• Thyroid function is vulnerable to endocrine disrupting chemicals (EDCs).
• Current 2D cell cultures lack the predictive power for accurate EDC safety assessment.
• Advanced 3D cell culture systems are needed to model thyroid follicular architecture and function.

Purpose of the Study:

• To develop a novel thyroid organoid-on-a-chip (OoC) device.
• To create a more physiologically relevant in vitro model for thyroid research.
• To enhance the evaluation of chemical compound safety and endocrine disruption.

Main Methods:

• Development of a microfluidic chip with polymeric membranous carriers.
• Incorporation of mouse embryonic stem cell-derived thyroid follicles.
• Utilizing a reversible seal for efficient loading and unloading of organoids.
• Conducting a 4-day experiment at a flow rate of 12 µL/min.

Main Results:

• The OoC model maintained high functionality, preserving key thyroid gene expression and follicular structure.
• Transcriptional analysis revealed activation of the aryl hydrocarbon receptor pathway upon benzo[k]fluoranthene exposure.
• The system demonstrated a physiologically relevant response to chemical exposure.

Conclusions:

• The developed OoC system serves as a valuable and physiologically relevant thyroid model.
• This advanced 3D model can significantly improve the testing of potential endocrine disrupting chemicals.
• The OoC platform offers enhanced predictive power for chemical safety assessments.