Descripción del proyecto
Modelos tridimensionales de la glándula tiroides para detectar alteradores endocrinos
En los ensayos celulares tridimensionales se replica con mayor fidelidad la estructura y la función del tejido nativo, con lo que se consiguen mejores modelos de prueba para llevar a cabo estudios de biología, bioquímica y descubrimiento farmacológico. En el proyecto SCREENED, financiado con fondos europeos, se trabaja en organoides de la glándula tiroides nativos, matrices descelularizadas o construcciones bioimpresas que albergan células específicas de tejidos concretos. Mediante estos ensayos, los investigadores analizan el efecto que tienen sobre la función tiroidea sustancias químicas que actúan como alteradores endocrinos, a fin de ofrecer una comprensión mecanicista de su modo de acción. Los resultados validarán la sensibilidad y especificidad de estos ensayos «in vitro», en comparación con los actuales cultivos celulares bidimensionales y los modelos animales.
Objetivo
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
Ámbito científico
Palabras clave
Programa(s)
Tema(s)
Convocatoria de propuestas
Consulte otros proyectos de esta convocatoriaConvocatoria de subcontratación
H2020-SC1-2018-Single-Stage-RTD
Régimen de financiación
RIA - Research and Innovation actionCoordinador
6200 MD Maastricht
Países Bajos