Scientists at the Wyss Institute have created a 3-dimensional in vitro model of the human blood-brain-barrier (BBB)-“on-a-chip.”  The device will make it possible for researchers to test drugs, chemicals, and disease factors that interact with the BBB, without using animals – and in a 3-dimensional environment that mimics that of the human BBB in vivo.

The BBB is a semi-permeable cellular structure that allows some nutrients and substances to enter the blood flow in the brain, and keeps other elements (such as bacteria and potential toxins) out. Because it is so effective, it can also prevent useful treatments from reaching targets in the brain. Researchers need to understand how and why certain substances can pass through the barrier, in part so they can design therapeutic drugs accordingly, and so they can design other substances to prevent neurotoxicity.

From the Wyss Institute press release: "These fluorescence confocal microscopy images show both a high magnification view (left) of a region of the human brain capillary endothelium within the endothelium lined tube (shown at lower magnification at right) that, in combination with surrounding human pericytes and astrocytes, comprise the blood-brain barrier (cell junctions linking adjacent endothelial cells are shown in magenta). " Credit: Wyss Institute at Harvard University

From the Wyss Institute press release: “These fluorescence confocal microscopy images show both a high magnification view (left) of a region of the human brain capillary endothelium within the endothelium lined tube (shown at lower magnification at right) that, in combination with surrounding human pericytes and astrocytes, comprise the blood-brain barrier (cell junctions linking adjacent endothelial cells are shown in magenta). ” Credit: Wyss Institute at Harvard University

To create the device, the Wyss Institute team carved a tiny channel in a polymer chip and filled it with a gel matrix containing human astrocytes, the cells that comprise the extra-tight “barrier” around blood vessels in the brain. Another channel was tunneled through this matrix and seeded with human pericyte cells (contractile cells which control the “gaps” through which substances can enter the neurological bloodstream) and then with human endothelial cells (the cells that line the interior of a blood vessel). The cells “self-assembled” into the same layers and connections they exhibit in blood vessels in vivo.

To test the model, the team introduced a protein known to cause inflammation – one that has been associated with a number of central nervous system diseases and disorders, including Alzheimer’s, multiple sclerosis, and stroke (among others). The in vitro BBB responded by producing protective proteins. The device can thus be used to study neuroinflammation, and to test new treatments.

Read more in the Wyss Institute’s press release.