Descripción del proyecto
Innovador modelo basado en un órgano tridimensional en un chip para estudiar la formación de metástasis de mama a hueso
El principal obstáculo para prevención de la elevada mortalidad del cáncer de mama es el conocimiento limitado sobre la forma en que las células del cáncer de mama metastatizan en zonas óseas. El objetivo del proyecto B2B, financiado con fondos europeos, es elaborar un modelo tridimensional (3D) pionero de metástasis espontánea de cáncer de mama para fines de investigación fundamental y cribaje de fármacos en un contexto fisiológico. Superará los inconvenientes de los modelos tradicionales «in vitro» e «in vivo» al imitar el sistema fisiológico de los órganos conectados. Los organoides de cáncer de mama cultivados se conectarán «in vitro» a tejidos óseos con médula ósea a través de un sistema fluídico de canalículos autoensamblados de estos organoides y un árbol macrovascular bioimpreso en 3D de vasos sanguíneos ramificados.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
Convocatoria de propuestas
Consulte otros proyectos de esta convocatoriaConvocatoria de subcontratación
H2020-FETOPEN-1-2016-2017
Régimen de financiación
RIA - Research and Innovation actionCoordinador
00185 Roma
Italia