Descrizione del progetto
Modello innovativo basato su organi 3D su chip per studiare la formazione di metastasi dal seno all’osso
Le limitate conoscenze riguardo alle modalità di metastatizzazione ossea delle cellule tumorali del seno costituiscono un ostacolo considerevole ai fini della prevenzione dell’elevata mortalità dovuta al carcinoma mammario. Il progetto B2B, finanziato dall’UE, intende sviluppare un modello tridimensionale, primo nel suo genere, di metastasi spontanee del carcinoma mammario nell’osso ai fini della ricerca di base e dello screening dei farmaci in un contesto fisiologico. Il progetto supererà gli inconvenienti dei tradizionali modelli in vitro e in vivo imitando il sistema fisiologico degli organi connessi. Organoidi coltivati del carcinoma mammario saranno collegati in vitro al tessuto osseo contenente midollo attraverso un sistema fluidico che coinvolge i capillari autoassemblati di questi organoidi e un albero macrovascolare artificiale 3D biostampato di vasi sanguigni ramificati.
Obiettivo
Cancer patients developing a metastatic disease are considered incurable. Breast cancer hits 1 woman in 8, and its most common metastatic site is the bone. A major hurdle to overcome breast cancer mortality is the lack of understanding of dynamics leading to the spread of breast cancer cells to the bone. Consequently, metastasis-suppressing agents have not been found to date, neither as newly developed drugs nor as repurposing of existing ones. The aim of the B2B device is to generate a first-of-a-kind 3D model of spontaneous breast cancer metastasis to the bone to dissect the complexity of the metastatic process and empower high-throughput drug screening in a physiological context. B2B will pursue its goal of developing a novel hybrid device able to 1) propagate patient-derived tumor organoids of clinically-relevant dimensions, with their own self-assembled micro-capillary networks, which are 2) continuously linked to a 3D bioprinted macro-vascular tree, organized in a hierarchical branched structure, connected in a closed circuit with 3) a vascularized marrow-containing bone ossicle, as the metastatic target. This is a unique approach, spanning the micro (single circulating metastatic cells, passing the endothelial barrier of capillary networks) to macro (tumor organoids and ossicles of clinically relevant size and tissue composition, connected by a hierarchically organized vascular tree) continuum to recapitulate spontaneous bone metastasis formation in breast cancer. This technology will transcend the limitations of current in vitro technologies, enabling physiological tissue-level complexity with organoids comprising several million cells, and its expected impact will be three-fold: to recapitulate the spontaneous metastatic process in breast cancer, to provide a breakthrough technology to investigate metastasis longitudinally and at the single cell level, and to lead to the identification of metastasis-suppressing therapies for breast cancer patients.
Campo scientifico
Parole chiave
Programma(i)
Invito a presentare proposte
Vedi altri progetti per questo bandoBando secondario
H2020-FETOPEN-1-2016-2017
Meccanismo di finanziamento
RIA - Research and Innovation actionCoordinatore
00185 Roma
Italia