Description du projet
Modèle innovant basé sur un organe sur puce en 3D pour étudier la formation de métastases du sein vers l’os
Un obstacle majeur à la prévention d’une mortalité élevée due au cancer du sein est la compréhension limitée de la manière dont les cellules cancéreuses du sein se métastasent vers les sites osseux. Le projet B2B, financé par l’UE, vise à développer un modèle 3D inédit de métastases spontanées du cancer du sein vers l’os, à des fins de recherche fondamentale et de dépistage de médicaments dans un contexte physiologique. Il permettra de surmonter les inconvénients des modèles traditionnels in vitro et in vivo en imitant le système physiologique d’organes connectés. Des cultures d’organoïdes de cancer du sein seront connectées in vitro au tissu osseux contenant de la moelle via un système fluidique impliquant les capillaires autoassemblés de ces organoïdes et un arbre macrovasculaire artificiel bio-imprimé en 3D composé de vaisseaux sanguins ramifiés.
Objectif
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.
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RIA - Research and Innovation actionCoordinateur
00185 Roma
Italie