A flow-enhanced microphysiological model of the human thyroid elicits a more organotypic response to endocrine disruptors

In this study, we aimed to engineer an in vitro model that better resembles the glandular architecture and hemodynamic perfusion of the native thyroid than current in vitro models, and that can better evaluate the effect of potential endocrine disrupting chemicals (EDCs) on the thyroid. We constructed a human thyroid-on-a-chip (ThyO) model by culturing NKX2-1wt-GFP/PAX8 human embryonic stem cell-derived thyroid organoids in an in-house developed microfluidic system for 7 days. We then performed fluorescence-activated cell sorting (FACS) of NKX2-1+ cells. We compared our ThyO model to static organoid controls using RNA sequencing. In addition, we mechanistically elucidated the effect of 7 days exposure to the EDC benzo(k)fluoranthene (BkF) on thyroid physiology both in the ThyO chip model and static organoids.