Projektbeschreibung
3D-Modelle der Schilddrüse zur Untersuchung endokriner Substanzen
Dreidimensionale Zellassays bilden die Struktur und Funktionsweise von natürlichem Gewebe detailgenauer ab und bieten sich dadurch als bessere Testmodelle für Biologie, Biochemie und Wirkstoffentwicklung an. Das EU-finanzierte Projekt SCREENED arbeitet an Organoiden der Schilddrüse, dezellularisierten Gerüsten sowie Konstrukten aus dem Bioprinter, die gewebespezifische Zellen enthalten. Anhand dieser Assays will das Forschungsteam die Wirkung endokrin wirksamer Substanzen auf die Schilddrüsenfunktion untersuchen und daraus ein mechanistisches Verständnis ihrer Funktionsweise erarbeiten. Die Ergebnisse werden die Sensitivität und Spezifität dieser In-vitro-Assays im Vergleich mit bestehenden zweidimensionalen Zellkulturen und Tiermodellen validieren.
Ziel
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
Wissenschaftliches Gebiet
Schlüsselbegriffe
Programm/Programme
Thema/Themen
Aufforderung zur Vorschlagseinreichung
Andere Projekte für diesen Aufruf anzeigenUnterauftrag
H2020-SC1-2018-Single-Stage-RTD
Finanzierungsplan
RIA - Research and Innovation actionKoordinator
6200 MD Maastricht
Niederlande