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


Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
21 May 2020
Historique:
received: 16 03 2020
revised: 04 05 2020
accepted: 14 05 2020
entrez: 28 5 2020
pubmed: 28 5 2020
medline: 17 2 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 32455722
pii: ijms21103648
doi: 10.3390/ijms21103648
pmc: PMC7279272
pii:
doi:

Substances chimiques

Endocrine Disruptors 0

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Horizon 2020 Framework Programme
ID : 825745

Déclaration de conflit d'intérêts

The authors declare no conflict of interest.

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Auteurs

Lorenzo Moroni (L)

MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Complex Tissue Regeneration, Maastricht University, 6229ET Maastricht, The Netherlands.

Fulvio Barbaro (F)

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.

Florian Caiment (F)

Toxicogenomics, Maastricht University, 6229ET Maastricht, The Netherlands.

Orla Coleman (O)

Atturos Ltd., c/o Conway Research Institute, University College Dublin, Dublin 4, Ireland.

Sabine Costagliola (S)

Institute of Interdisciplinary Research in Molecular Human Biology (IRIBHM), Université Libre de Bruxelles, 1050 Brussels, Belgium.

Giusy Di Conza (GD)

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.

Lisa Elviri (L)

Food and Drug Department, University of Parma, 43121 Parma, Italy.

Stefan Giselbrecht (S)

MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Instruct Biomaterials Engineering, Maastricht University, 6229ET Maastricht, The Netherlands.

Christian Krause (C)

PreSens Precision Sensing GmbH, 93053 Regensburg, Germany.

Carlos Mota (C)

MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Complex Tissue Regeneration, Maastricht University, 6229ET Maastricht, The Netherlands.

Marta Nazzari (M)

Toxicogenomics, Maastricht University, 6229ET Maastricht, The Netherlands.

Stephen R Pennington (SR)

Atturos Ltd., c/o Conway Research Institute, University College Dublin, Dublin 4, Ireland.
UCD Conway Institute, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.

Annette Ringwald (A)

ARTTIC, 58A rue du Dessous des Berges, 75013 Paris, France.

Monica Sandri (M)

Institute of Science and Technology for Ceramics, National Research Council of Italy (ISTEC-CNR), 48018 Faenza, Italy.

Simon Thomas (S)

Cyprotex Discovery Ltd., No. 24 Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.

James Waddington (J)

UCD Conway Institute, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.

Roberto Toni (R)

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.
Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center - Tufts University School of Medicine, Boston, MA 02111, USA.

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