Modeling Neuroimmunological Interactions at the Blood-Brain Barrier Using In Vitro 3D Human Organoids: Inflammation...

Area of Science:

• Neuroscience
• Immunology
• Biotechnology

Background:

• Central nervous system diseases often involve blood-brain barrier (BBB) disruption and immune cell infiltration.
• Targeting immune cell transmigration across the BBB is a promising therapeutic strategy.

Purpose of the Study:

• To develop and validate a 3D human BBB spheroidal model for studying immune cell transmigration.
• To assess the model's utility in simulating normal and pathological conditions, including inflammation and ischemia-reperfusion injury (IRI).

Main Methods:

• A 3D human BBB spheroidal model was created using six brain cell types: endothelial cells, pericytes, astrocytes, microglia, oligodendrocytes, and neural progenitor cells.
• The model was used to test CD4+ T-cell transmigration under normal, inflammatory, and hypoxia-reperfusion conditions.
• Changes in cell adhesion molecules and tight junction expression were analyzed.

Main Results:

• The 3D BBB model accurately recapitulated barrier features under normal and pathological states.
• Proinflammatory cytokines and hypoxia disrupted the BBB, increasing permeability and decreasing tight junctions.
• Immune cell transmigration was enhanced by inflammation and reperfusion, correlating with increased cell adhesion molecules.

Conclusions:

• The 3D human BBB model is a valuable tool for studying neuroimmune interactions and BBB pathophysiology.
• The model can be utilized for high-throughput screening of therapeutic targets aimed at modulating immune cell transmigration into the brain.