Thyroid-on-a-chip: An Organoid Platform For In Vitro Assessment of Endocrine Disruption

The thyroid is a glandular tissue in the human body in which the function can be severely affected by endocrine disrupting chemicals (EDCs). Current in vitro assays to test endocrine disruption by chemical compounds are largely based on 2D thyroid cell cultures, which often fail to precisely evaluate the safety of these compounds. New and more advanced 3D cell culture systems are urgently needed to better recapitulate the thyroid follicular architecture and functions and help to improve the predictive power of such assays. Here, we describe the development of a thyroid organoid-on-a-chip (OoC) device using polymeric membranous carriers. Mouse embryonic stem cell (ESC)-derived thyroid follicles were incorporated in a microfluidic chip for a 4-day experiment at a flow rate of 12 μL/min. A reversible seal provided a leak-tight sealing while enabling quick and easy loading/unloading of thyroid follicles. The OoC model showed a high degree of functionality, where organoids retained expression of key thyroid genes and a typical follicular structure. Finally, transcriptional changes following benzo[k]fluoranthene (BKF) exposure in the OoC device demonstrated activation of the xenobiotic aryl hydrocarbon receptor (AhR) pathway. Altogether, this OoC system is a physiologically relevant thyroid model, which will represent a valuable tool to test potential EDCs. This article is protected by copyright. All rights reserved.