Mutations in the NOTCH3 gene affect approximately 1 in 3 individuals worldwide and are the leading cause of hereditary cerebral small vessel disease, which can lead to stroke and vascular dementia. This project focuses on studying the disease in the lab using a 3D Vessel-on-Chip model with patient cells. This technology enables the creation of a 3D model of patient blood vessels, allowing researchers to observe how the disease develops.
Impact
Studying disease mechanisms that occur in patients suffering stroke and vascular dementia is challenging due to the reliance on autospy material for isolating and investigating brain blood vessels. This project provides an unexplored opportunity to gain new insights into the disease processes in a non-invasive manner and serve as future platform for testing therapeutics.
reNEW research
The 3D model with patient cells is fully developed and provided new understandings on how the disease cells behave in this system. This allowed to study novel disease markers with patient lines and validate those results with patient primary brain blood vessel cells and brain blood vessel tissue.
Image description
Patient vascular smooth muscle cells showing different identities: mature (magenta) and immature (blue). Cells present a more mature aspect upon contact with 3D vasculature (white).
Credits
Marc Vila Cuenca, Senior Postdoc, Orlova Lab, reNEW Leiden.
