A microfluidic thyroid-liver platform to assess chemical safety in humans

A rodent thyroid-liver chip to capture thyroid toxicity on organ functional level

“…Moreover, the individual compounds induced different effect patterns including clear evidence of a known species-specific induction of CYP3A1 by RIF and PCN (Lu and Li, 2001;Li et al, 2009). Interestingly, PCN which strongly induced liver enzyme activity in the rat liver model did not induce comparable effects in a similar human liver chip developed in parallel (Kühnlenz et al, 2022). In contrast, RIF induced CYP3A1 enzyme activity in the human liver model without increasing liver enzyme activity or gT4 formation in the rat liver model.…”

“…We have therefore aimed to develop a rat thyroid-liver chip for a simultaneous investigation of direct and indirect mechanisms of thyroid perturbation on organ-level functions. The combined application with a very similar human thyroid-liver model established in parallel (Kühnlenz et al, 2022) will allow identifying potential species differences.…”

“…At its current stage, the thyroid-liver organ chip demonstrates the feasibility of simultaneously capturing direct and indirect mechanisms of thyroid perturbation on a functional level in vitro. Furthermore, this model, in conjunction with a very similar parallel established human thyroid-liver model (Kühnlenz et al, 2022), allows to directly test and investigate potential species differences of rat and human thyroid disruption in response to compound treatment. Notwithstanding, further efforts are still needed to optimize and qualify the established model prior be taken into consideration for initial chemical screening in a regulatory context.…”

“…We here introduce a rat thyroid-liver chip that enables simultaneous identification of direct and indirect (liver-mediated) thyroid perturbation on organ-level functions in vitro. A second manuscript describes our work toward a human thyroid-liver chip (Kühnlenz et al, 2022). The presented microfluidic model consisting of primary rat thyroid follicles and liver 3D spheroids maintain a tissue-specific phenotype for up to 21 days.…”

The effects of hexabromocyclododecane on the transcriptome and hepatic enzyme activity in three human HepaRG-based models

“…These authors showed that PCB-153, a known thyroid hormone disruptor in rats (Liu et al, 2012), induced T4 glucuronidation in PHH. More recently, 3D models of HepaRG cells were tested on their capacity to synthesize thyroid binding serum proteins and metabolize T4 through glucuronide or sulfate conjugation (Kühnlenz et al, 2022). This study illustrated the potential of using human in vitro hepatocyte models for screening chemicals disruption of T4 metabolism.…”