Type project: R&D
Bone metastasis chip with microphysiological circulation for cancer profiling (OSCAR)
Cancer treatments have improved significantly over the past decades. However, metastasis, the spreading of tumour cells to distant organs, remains incurable and represents the major cause of death of cancer patients. Skeletal metastasis is frequent in multiple cancer types, particularly in prostate (85%) breast cancer (70%) patients, which strongly impact the patients’ quality of life. We do not understand what mechanisms drive circulating tumour cells (CTCs) extravasation from the blood into the soft and nutrient-rich bone marrow, and to invade towards the stiffer bone compartment, where they establish specific interactions with bone-forming (osteoblasts) and bone-degrading (osteoclasts) cell types. The understanding of the cancer-specific crosstalk and remodelling of the bone environment is crucial to establish better options for prevention, prediction, and treatment of bone metastases. Current bone models lack the important vascularized bone marrow compartment, thereby neglecting the contribution of the bone marrow as transition site with its unique mechanical and physical properties. The aim of this project is to develop a “bone-metastasis-chip” (OSCAR) with a recirculation system (CRIS) that recapitulates the passage of cancer cells from the blood stream to stiff bone structures to profile the CTC-specific crosstalk and bone marrow changes. We will adopt available chip designs and modify them according to the requirements of OSCAR. CRIS will be designed with an emphasis on compatibility with circulating cells and easy operation with a small footprint to scale up experiments. An oxygen gradient will be established in OSCAR and measured using commercial sensors. This project will deliver an advanced and tuneable bone-on-chip system that faithfully mimics the anatomy and physiology of human bone allowing the study of CTC behaviour during the earliest stages of bone metastatic development. Importantly, OSCAR and the knowledge generated has pan-cancer relevance with application in a broad field of preclinical research.
Azar Innovations is committed to perform R&D in this project with technical advice from TU/e and perfusion solutions of Dolomite Microfluidics, and develop a fit-for-purpose bone metastasis chip.
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