A microengineered Brain-Chip to model neuroinflammation in humans.

Area of Science:

• Neuroscience
• Biotechnology
• Drug Development

Background:

• Species differences in brain and blood-brain barrier (BBB) biology hinder the translation of findings from animal models to human therapeutics for brain diseases.
• Existing microphysiological systems (MPS) often lack the complexity and physiological relevance needed to accurately model human brain conditions.

Purpose of the Study:

• To develop a human organotypic Brain-Chip microphysiological system (MPS) that accurately recapitulates blood-brain barrier (BBB) function and neuroinflammation.
• To enhance the clinical mimicry of brain disease models for improved understanding of cell-cell interactions and therapeutic development.

Main Methods:

• Engineered a human organotypic Brain-Chip MPS incorporating endothelial-like cells, pericytes, glia, and cortical neurons.
• Maintained blood-brain barrier (BBB) permeability at in vivo relevant levels.
• Utilized transcriptomic profiling and exposure to TNF-α to assess inflammatory responses and barrier integrity.

Main Results:

• The developed Brain-Chip demonstrated significant improvements in clinical mimicry compared to previous MPS and Transwell cultures.
• Transcriptomic profiling showed advanced similarity to the human adult cortex and enrichment in key neurobiological pathways.
• Exposure to TNF-α successfully recreated an inflammatory environment, characterized by glia activation, increased proinflammatory cytokine release, and compromised barrier permeability.

Conclusions:

• The developed human Brain-Chip MPS provides a robust platform for mechanistic understanding of cell-cell interactions and blood-brain barrier (BBB) function during neuroinflammation.
• This model offers enhanced clinical relevance for studying brain diseases and developing novel therapeutics.
• The system represents a significant advancement over existing models for brain research.