An engineered neurovascular unit for modeling neuroinflammation.

Area of Science:

• Neuroscience
• Cell Biology
• Biomedical Engineering

Background:

• The neurovascular unit (NVU) is crucial for brain homeostasis and function.
• Dysfunction of the NVU is implicated in central nervous system disorders like Alzheimer's disease and stroke.
• There is a need for advanced in vitro models to study NVU physiology and pathology.

Purpose of the Study:

• To develop a novel, three-dimensional (3D) human cell-based in vitro model of the neurovascular unit (NVU).
• To investigate the impact of this 3D co-culture model on the maturation of brain endothelial barrier function.
• To assess the utility of the model in studying inflammatory responses and for drug development.

Main Methods:

• Generation of a 3D immortalized human cell-based NVU model using a collagen matrix.
• Incorporation of six key cell types comprising the NVU: brain endothelial cells, astrocytes, pericytes, neurons, microglia, and oligodendrocytes.
• Co-culture of these cells around a perfusable brain endothelium to mimic the in vivo microenvironment.

Main Results:

• The 3D NVU model demonstrated significantly improved maturation of barrier function.
• Secreted cytokines from NVU-composing cells supported the enhanced barrier function.
• NVU-composing cells in the model effectively alleviated lipopolysaccharide-induced inflammatory responses.

Conclusions:

• The developed human cell-based 3D NVU in vitro model accurately recapitulates key aspects of the brain microenvironment.
• This model facilitates the study of human brain physiological and pathological mechanisms.
• The model is suitable for high-content analysis in drug development, enabling safety and efficacy evaluations.