Abstract:
The Horizon 2020 European Project SCREENED focuses on the development of in vitro 3D assays based on 3D organoids engineered with mammalian thyroid cells, to screen for the effect of low-dose Endocrine Disruptors (EDs). Recently, in accordance with the requirements set by the EU Joint Research Center (JRC), we developed the readiness criteria for a new in vitro template based on 3D thyroid organoids self-assembled from adult rat thyroid stem cells, later differentiated to thyroid follicular cells. Endpoints for the assay are quantitative proteomic data presented in matrix form (heat map) ensuing from the challenge of organoids with different EDs in a range of supposedly effective concentrations, compared to unchallenged or test-substance challenged controls. The resulting high dimensional data panels were confronted using algorithm-based procedures of the Perseus software (version1.6.15.0.) to establish a statistically significant difference in molecular quantitities (ED challenged samples vs controls). However, a search for statistical approaches aimed at detecting average and discrete molecular differences is in progress. In addition, an implementation of a previously developed computational kernel for near fractal growth of the human thyroid lobe vasculature inside a simulated thyroid lobe profile yielded a virtual reconstruction of its 2nd to 4th order arteries. Preliminary comparisons between percentages of simulated vs real cadaveric human thyroid lobe vessels suggested a similarity tendency, though some differences highlight the need for accurate statistical approaches to weight their significance. Collectively, this result encourages to pursue the feasibility of biomaterial reproduction with additive layer manufacturing of this vascular network, thus providing a reticular scaffold to engineer, ex situ, a 3D human thyroid gland as a surrogate organ for in vitro ED tests on the human thyroid function.
[ This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 825745 ]
Links:
https://www.unipr.it/notizie/interferenti-endocrini-luniversita-di-parma-vincitrice-di-un-finanziamento-europeo-horizon
https://magazine.unibo.it/archivio/2019/02/06/test-sulla-tirode-umana-grazie-a-modelli-3d-una-docente-unibo-partecipa-al-progetto-screened
https://mc.unipr.it/it/laboratorio-di-morfologia-rigenerativa-e-strutture-bioartificiali
Organizzatore
Giulia Spaletta