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Open AccessProject Report

SCREENED: A Multistage Model of Thyroid Gland Function for Screening Endocrine-Disrupting Chemicals in a Biologically Sex-Specific Manner

1
MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Complex Tissue Regeneration, Maastricht University, 6229ET Maastricht, The Netherlands
2
Department of Medicine and Surgery—DIMEC, Unit of Biomedical, Biotechnological and Translational Sciences (S.BI.BI.T.), Laboratory of Regenerative Morphology and Bioartificial Structures (Re.Mo.Bio.S. Lab.), University of Parma, 43121 Parma, Italy
3
Toxicogenomics, Maastricht University, 6229ET Maastricht, The Netherlands
4
Atturos Ltd., c/o Conway Research Institute, University College Dublin, Dublin 4, Ireland
5
Institute of Interdisciplinary Research in Molecular Human Biology (IRIBHM), Université Libre de Bruxelles, 1050 Brussels, Belgium
6
Food and Drug Department, University of Parma, 43121 Parma, Italy
7
MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Instruct Biomaterials Engineering, Maastricht University, 6229ET Maastricht, The Netherlands
8
PreSens Precision Sensing GmbH, 93053 Regensburg, Germany
9
UCD Conway Institute, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland
10
ARTTIC, 58A rue du Dessous des Berges, 75013 Paris, France
11
Institute of Science and Technology for Ceramics, National Research Council of Italy (ISTEC-CNR), 48018 Faenza, Italy
12
Cyprotex Discovery Ltd., No. 24 Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
13
Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center - Tufts University School of Medicine, Boston, MA 02111, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(10), 3648; https://doi.org/10.3390/ijms21103648
Received: 16 March 2020 / Revised: 4 May 2020 / Accepted: 14 May 2020 / Published: 21 May 2020
(This article belongs to the Special Issue Advances in the Research of Endocrine Disrupting Chemicals 2.0)
Endocrine disruptors (EDs) are chemicals that contribute to health problems by interfering with the physiological production and target effects of hormones, with proven impacts on a number of endocrine systems including the thyroid gland. Exposure to EDs has also been associated with impairment of the reproductive system and incidence in occurrence of obesity, type 2 diabetes, and cardiovascular diseases during ageing. SCREENED aims at developing in vitro assays based on rodent and human thyroid cells organized in three different three-dimensional (3D) constructs. Due to different levels of anatomical complexity, each of these constructs has the potential to increasingly mimic the structure and function of the native thyroid gland, ultimately achieving relevant features of its 3D organization including: (1) a 3D organoid based on stem cell-derived thyrocytes, (2) a 3D organoid based on a decellularized thyroid lobe stromal matrix repopulated with stem cell-derived thyrocytes, and (3) a bioprinted organoid based on stem cell-derived thyrocytes able to mimic the spatial and geometrical features of a native thyroid gland. These 3D constructs 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. Finally, these 3D constructs will be used to screen the effect of EDs on the thyroid function in a unique biological sex-specific manner. Their performance will be assessed individually, in comparison with each other, and against in vivo studies. The resulting 3D assays are expected to yield responses to low doses of different EDs, with sensitivity and specificity higher than that of classical 2D in vitro assays and animal models. Supporting the “Adverse Outcome Pathway” concept, proteogenomic analysis and biological computational modelling of the underlying mode of action of the tested EDs will be pursued to gain a mechanistic understanding of the chain of events from exposure to adverse toxic effects on thyroid function. For future uptake, SCREENED will engage discussion with relevant stakeholder groups, including regulatory bodies and industry, to ensure that the assays will fit with purposes of ED safety assessment. In this project review, we will briefly discuss the current state of the art in cellular assays of EDs and how our project aims at further advancing the field of cellular assays for EDs interfering with the thyroid gland. View Full-Text
Keywords: endocrine disruptors; in vitro models; bioprinting; omics; decellularization; organoids endocrine disruptors; in vitro models; bioprinting; omics; decellularization; organoids
MDPI and ACS Style

Moroni, L.; Barbaro, F.; Caiment, F.; Coleman, O.; Costagliola, S.; Di Conza, G.; Elviri, L.; Giselbrecht, S.; Krause, C.; Mota, C.; Nazzari, M.; Pennington, S.R.; Ringwald, A.; Sandri, M.; Thomas, S.; Waddington, J.; Toni, R. SCREENED: A Multistage Model of Thyroid Gland Function for Screening Endocrine-Disrupting Chemicals in a Biologically Sex-Specific Manner. Int. J. Mol. Sci. 2020, 21, 3648.

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