Descrizione del progetto
Modelli tridimensionali della ghiandola tiroidea per lo screening degli interferenti endocrini
I saggi cellulari tridimensionali imitano la struttura e la funzione dei tessuti nativi in modo più fedele rispetto alle soluzioni bidimensionali, offrendo modelli di prova migliori per gli studi nei campi della biologia, della biochimica e della scoperta di farmaci. Il progetto SCREENED, finanziato dall’UE, sta lavorando a organoidi derivati dalla ghiandola tiroidea naturale, impalcature decellularizzate o strutture biostampate in grado di ospitare cellule specifiche per tessuto. Avvalendosi di questi saggi, i ricercatori stanno esplorando l’effetto esercitato dalle sostanze chimiche interferenti endocrine sulla funzione della tiroide, offrendo una comprensione meccanicistica della loro modalità d’azione. I risultati convalideranno la sensibilità e la specificità di questi saggi in vitro in confronto alle colture cellulari bidimensionali e ai modelli animali esistenti.
Obiettivo
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
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Vedi altri progetti per questo bandoBando secondario
H2020-SC1-2018-Single-Stage-RTD
Meccanismo di finanziamento
RIA - Research and Innovation actionCoordinatore
6200 MD Maastricht
Paesi Bassi