Description du projet
Des modèles 3D de la glande thyroïde pour le dépistage des perturbateurs endocriniens
Les tests cellulaires en trois dimensions (3D) permettent de reproduire avec davantage de fidélité la structure et la fonction des tissus natifs, offrant ainsi de meilleurs modèles de test pour la biologie, la biochimie et les études de découverte de médicaments. Le projet SCREENED, financé par l’UE, travaille sur des organoïdes natifs de la glande thyroïde, des échafaudages décellularisés ou des constructions bio‑imprimées qui abritent des cellules spécifiques aux tissus. Avec ces tests, les chercheurs étudient l’effet des substances chimiques perturbatrices du système endocrinien sur la fonction thyroïdienne, ce qui permet de comprendre mécaniquement leur mode d’action. Les résultats permettront de valider la sensibilité et la spécificité de ces essais in vitro par rapport aux cultures de cellules 2D et aux modèles animaux existants.
Objectif
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
Champ scientifique
Mots‑clés
Programme(s)
Thème(s)
Régime de financement
RIA - Research and Innovation actionCoordinateur
6200 MD Maastricht
Pays-Bas