Back to Search Start Over

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

Authors :
Moroni, Lorenzo
Barbaro, Fulvio
Caiment, Florian
Coleman, Orla
Costagliola, Sabine
Conza, Giusy Di
Elviri, Lisa
Giselbrecht, Stefan
Krause, Christian
Mota, Carlos
Nazzari, Marta
Pennington, Stephen SR
Ringwald, Annette
Sandri, Monica
Thomas, Simon
Waddington, James
Toni, Roberto
Moroni, Lorenzo
Barbaro, Fulvio
Caiment, Florian
Coleman, Orla
Costagliola, Sabine
Conza, Giusy Di
Elviri, Lisa
Giselbrecht, Stefan
Krause, Christian
Mota, Carlos
Nazzari, Marta
Pennington, Stephen SR
Ringwald, Annette
Sandri, Monica
Thomas, Simon
Waddington, James
Toni, Roberto
Source :
International journal of molecular sciences, 21 (10
Publication Year :
2020

Abstract

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, proteoge<br />SCOPUS: ar.j<br />info:eu-repo/semantics/published

Details

Database :
OAIster
Journal :
International journal of molecular sciences, 21 (10
Notes :
1 full-text file(s): application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1192459342
Document Type :
Electronic Resource