3D Self-Organized Human Blood-Brain Barrier in a Microfluidic Chip

Area of Science:

• Neuroscience
• Biotechnology
• Pharmacology

Background:

• Preclinical blood-brain barrier (BBB) models are crucial for studying brain transport and drug delivery.
• Conventional Transwell assays lack the 3D architecture and critical cellular interactions of the brain microvasculature.
• Developing a more physiologically relevant in vitro BBB model is essential for accurate research.

Purpose of the Study:

• To develop and characterize a novel in vitro blood-brain barrier (BBB) model.
• To create a model that recapitulates key features of the human brain microvasculature, including transporters, tight junctions, and extracellular matrix.
• To establish a platform for screening brain-targeting drugs and investigating neurovascular functions.

Main Methods:

• Coculture of human-induced pluripotent stem cell-derived endothelial cells (iPSC-ECs), brain pericytes (PCs), and astrocytes (ACs) within a microfluidic device.
• Formation of a functional BBB model expressing essential neurovascular components.
• Assessment of brain vascular permeability and comparison with conventional in vitro models and in vivo data.

Main Results:

• The microfluidic BBB model successfully expressed neurovascular membrane transporters, tight junction proteins, and extracellular matrix proteins.
• The model demonstrated human brain vascular permeability values lower than conventional in vitro models.
• The measured permeability was comparable to in vivo measurements in rat brains, indicating high fidelity.

Conclusions:

• The developed microfluidic BBB model offers a more accurate representation of the human brain microvasculature.
• This advanced in vitro model can be effectively utilized for screening brain-penetrant drugs and for studying complex neurovascular functions.
• The model provides a valuable tool for preclinical research in neuroscience and drug development.