A Human Neurovascular Unit On-a-Chip

Area of Science:

• Neuroscience
• Biomedical Engineering
• Cell Biology

Background:

• The central nervous system (CNS) relies on the blood-brain barrier (BBB) for protection and homeostasis.
• The BBB's restrictive nature impedes drug delivery for treating neurological disorders and brain tumors.
• Existing in vivo and in vitro models have limitations in replicating the human BBB's environment.

Purpose of the Study:

• To develop an advanced microfluidic model of the human neurovascular unit.
• To overcome limitations of current models in simulating the human BBB.
• To create a more accurate platform for studying BBB function and improving therapeutic strategies.

Main Methods:

• Established a microfluidic device containing a co-culture of human cerebral endothelial cells (hCMEC-D3), brain pericytes (hBMVPC), astrocytes (hiPSC-AC), and neurons (hiPSC-N).
• Utilized fluorescent cell-specific markers and confocal microscopy to visualize cellular morphology.
• Assessed barrier function by measuring the permeation of fluorescent solutes with varying molecular weights.

Main Results:

• Successfully cultured a multi-cellular neurovascular unit within a microfluidic system.
• Visualized the distinct physiological morphology of endothelial cells, pericytes, astrocytes, and neurons.
• Demonstrated selective permeability of the model to fluorescent solutes, confirming its function as a barrier.

Conclusions:

• The developed microfluidic model effectively replicates key aspects of the human blood-brain barrier.
• This model offers a more physiologically relevant platform for studying BBB mechanisms.
• It holds potential for advancing drug discovery and therapeutic development for CNS diseases.