Vascular-Perfusable Human 3D Brain-on-Chip.

Area of Science:

• Neuroscience
• Biotechnology
• Stem Cell Biology

Background:

• The human blood-brain barrier (BBB) presents challenges for neurological disease treatment and modeling.
• Existing animal and in-vitro models have limitations in replicating human BBB complexity and genetics.
• Current 3D BBB-on-chip models often lack the full complement of brain cell types.

Purpose of the Study:

• To develop a comprehensive 3D Brain-Chip system using human induced pluripotent stem cells (iPSCs).
• To incorporate multiple brain cell types for a more accurate model of the human neurovascular unit.
• To create a platform for studying genetic risk factors and testing neurological therapies.

Main Methods:

• Engineered a GelChip microfluidic platform using 3D printing and hydrogels.
• Co-cultured iPSC-derived endothelial cells, pericytes, astrocytes, neurons, microglia, and oligodendroglia.
• Modeled the brain microvasculature, including the APOE4 variant associated with Alzheimer's disease.

Main Results:

• Successfully developed a multicellular 3D Brain-Chip system with iPSC-derived brain cells.
• Characterized the co-cultured iPSC-derived brain-on-chips.
• Demonstrated the ability to model human genetic risk factors like APOE4 in the BBB.

Conclusions:

• The developed 3D Brain-Chip system offers a versatile platform for neurological disease research.
• This model can assess BBB function, investigate disease mechanisms, and screen therapeutics.
• It advances the development of more effective treatments for neurological disorders by providing a human-relevant model.