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

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
Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

Coordinator

UNIVERSITEIT MAASTRICHT

Address

Minderbroedersberg 4-6
6200 Md Maastricht

Netherlands

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 795 750

Participants (8)

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UNIVERSITA DEGLI STUDI DI PARMA

Italy

EU Contribution

€ 1 000 000

UNIVERSITE LIBRE DE BRUXELLES

Belgium

EU Contribution

€ 499 200

CONSIGLIO NAZIONALE DELLE RICERCHE

Italy

EU Contribution

€ 400 000

PRESENS PRECISION SENSING GMBH

Germany

EU Contribution

€ 493 750

UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN

Ireland

EU Contribution

€ 300 167,50

ATTUROS LIMITED

Ireland

EU Contribution

€ 250 000

ARTTIC

France

EU Contribution

€ 564 781,25

CYPROTEX DISCOVERY LIMITED

United Kingdom

EU Contribution

€ 351 440

Project information

Grant agreement ID: 825745

Status

Ongoing project

  • Start date

    1 January 2019

  • End date

    31 December 2023

Funded under:

H2020-EU.3.1.1.

  • Overall budget:

    € 5 655 088,75

  • EU contribution

    € 5 655 088,75

Coordinated by:

UNIVERSITEIT MAASTRICHT

Netherlands