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CORDIS

A multistage model of thyroid gland function for screening endocrine-disrupting chemicals in a biologically sex-specific manner

Project description

3D thyroid gland models for screening endocrine disruptors

Three-dimensional (3D) cell assays more faithfully mimic the structure and function of native tissue, offering better test-models for biology, biochemistry and drug discovery studies. The EU-funded SCREENED project is working on native thyroid gland organoids, decellularised scaffolds or bioprinted constructs that house tissue-specific cells. Using these assays, researchers are investigating the effect of endocrine-disrupting chemicals on thyroid function offering a mechanistic understanding of their mode of action. Results will validate the sensitivity and specificity of these in vitro assays compared to existing 2D cell cultures and animal models.

Objective

SCREENED will develop 3 different three-dimensional (3D) in vitro assays based on rodent and human thyroid cell constructs. At different level of anatomical complexity, these assays will increasingly mimic the structure and function of the native thyroid gland, ultimately achieving the replication of its vascular anatomy and morphogenetic characteristics: 1) a 3D organoid based on stem-cell derived thyroid cells, 2) a decellularized scaffold able to reproduce the biological composition of a native thyroid, repopulated by the 3D organoids, and 3) a bioprinted construct with the 3D organoids able to mimic the spatial and geometrical architecture of a native thyroid. These 3D assays will be hosted in a modular microbioreactor equipped with innovative sensing technology and enabling precise control of cell culture conditions. New superparamagnetic biocompatible and biomimetic particles will be used to produce “magnetic cells” to support precise spatiotemporal homing of the cells in the 3D decellularized and bioprinted constructs.
The 3D assays will be used to screen the effect of endocrine disruptors (EDs) on the thyroid function in a unique biological sex-specific approach. Their performance will be assessed individually, in comparison with each other, and against in vivo studies. The 3D assays are expected to predict with more sensitivity and specificity the thyroid responses to different classes of EDs at low doses, compared to classical 2D in vitro assays or animal models.
Supporting the “Adverse Outcome Pathway” concept, proteogenomics analysis and biological modelling of the underlying mode of action will be used to gain a mechanistic understanding of the chain of events from exposure to adverse effects on thyroid development and function.
For future uptake, SCREENED will engage discussion with relevant stakeholder groups, including regulatory bodies and industry, to ensure that the assays are fit for purpose for ED safety assessment

Call for proposal

H2020-SC1-BHC-2018-2020

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Sub call

H2020-SC1-2018-Single-Stage-RTD

Coordinator

UNIVERSITEIT MAASTRICHT
Net EU contribution
€ 1 964 076,82
Address
MINDERBROEDERSBERG 4
6200 MD Maastricht
Netherlands

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Region
Zuid-Nederland Limburg (NL) Zuid-Limburg
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 1 964 076,82

Participants (8)