Generating a Blood-Brain Barrier Chip Using iPSC-derived Precursor Cells

Take a microfluidic chip with superimposed, matrix-coated channels separated by a porous membrane.

Seed iPSC-derived neural progenitor cells in the upper channel. Incubate for cell adherence, then wash to remove the unattached cells.

Next, seed iPSC-derived brain microvascular endothelial cells in the bottom channel.

Invert the chip and incubate it to attach the endothelial cells to the membrane side of the bottom channel.

Next, flip the chip to attach cells to the lower side of the channel, forming a monolayer tube-like structure. Wash both channels with cell-specific media. 

Continuously flow a neural differentiation medium in the upper channel and an endothelial cell medium in the lower channel.

Endothelial cells utilize growth factors from the medium to mature and form tight junctions resembling a blood vessel, forming the blood side.

Neurotrophic factors drive the differentiation of neural progenitor cells into various brain cells, forming the brain side. These cells interact with the endothelial cells, creating a blood-brain barrier on the chip.