Project description
3D microfluidic neurovascular unit model to study brain cell responses to inflammation
Neurological disorders are the leading cause of disability in the modern world and are associated with impaired blood-brain barrier (BBB) function. Presently, neither animal nor human cell models of the BBB exist to mimic the barrier and transporter functions. The EU-funded NVU-Chip project aims to develop a 3D neurovascular unit (NVU) model to study cell type-specific responses in the presence of inflammatory stimuli. The project objective is to recreate the cellular environment inside a microfluidic device, recapitulating human NVU and incorporating cyclic mechanical strain. This approach combines state-of-the-art stem cell technologies to obtain necessary cells and advanced microfabrication to design and build the microfluidic chips using the extracellular matrix coatings for co-culturing all cell types in the same device.
Objective
Neurological disorders affect many people's life, contributing to significant mortality and morbidity in the modern world, with 16.5% of global deaths and are the leading cause of disability, affecting 276 million people's daily lives. Many of these diseases, including Alzheimer’s and Multiple Sclerosis, are related with the impaired blood-brain barrier (BBB) function. Unfortunately, neither animal models of the neurovascular unit (NVU) nor in vitro cultures of primary or immortalized human brain microvascular endothelial cells (BMVECs) alone effectively mimic the barrier, and transporter functions of the BBB observed in humans. Thus, there is a great need for human NVU models to recapitulate in vivo human physiology in health and disease conditions and understand the cellular mechanisms and changes in disease conditions. This project aims to develop a 3D NVU model to identify the cell-type-specific responses to diverse inflammatory stimuli in the NVU.
The NVU-Chip project will the first model providing such a complex cellular environment in a unique microfluidic device to fully recapitulating human NVU in vitro utilizing relevant mechanobiological forces. Additionally, The NVU-Chip will improve the state-of-the-art by incorporating cyclic mechanical strain in a BBB model for the first time. This project will combine and amend the state-of-the-art stem cell technologies to differentiate all brain cells, and advanced microfabrication approaches to design and fabricate the microfluidic chips using the most appropriate materials ECM coatings for co-culturing all cell types in the same device. The human-based NVU-Chip model will also give a new approach for studying cellular responses to diverse inflammatory stimuli, identifying key inflammatory factors of CNS related diseases.
Outcomes of the NVU-Chip project will enhance the existing knowledge and technologies, yielding high-impact journal publications, as well as potential commercial product in the long term.
Fields of science
- natural sciencesphysical sciencesclassical mechanicsfluid mechanicsmicrofluidics
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- medical and health sciencesbasic medicineneurologymultiple sclerosis
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- medical and health sciencesbasic medicinephysiology
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Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
34956 Istanbul
Türkiye