Blood-Brain Barrier on a Chip

Blood-Brain Barrier on a Chip

By Vidhya Sivakumaran

The blood-brain barrier (BBB) is a highly selective semipermeable membrane barrier, which allows some materials to cross while blocking others. It is formed by endothelial cells connected by tight junctions. This network of specialized cells surrounds the arteries and veins that provide the brain with nutrients and protection. In recent years, medical researchers have improved their understanding of how the blood-brain barrier works, as well as implicated it in a broad range of brain disorders, from stroke to blunt force trauma to brain inflammation. But as important as the blood-brain barrier is, scientists hadn’t been able to create laboratory models that can reproduce the critical blood flow effects or support the different cell types found in the human blood-brain barrier—until recently.

Organ-on-a-Chip for Blood-Brain Barrier: The NeuroVascular Unit (NVU)

At Vanderbilt University, researchers have developed a microfluidic device that overcomes the limitations of previous published models and mimics the blood-brain barrier. This organ on a chip was used to study brain inflammation, also dubbed the “silent killer”, because it doesn’t cause any pain but contributes to neurodegenerative conditions, such as Parkinson’s and Alzheimer’s. The device, called the NeuroVascular Unit (NVU) on a chip, conquers many of the problems faced by old models.

The NVU consists of a small cavity that is about one-millionth of the size of a human brain. It contains a synthetic, thin porous membrane that divides the cavity into an upper chamber, which acts similarly to the brain side of the barrier, and a lower chamber, which acts as the blood or vascular side. Microchannels on either side are hooked up to micro-pumps that allow them to be independently perfused and sampled. In order to create the artificial blood-brain barrier, scientists inject the vascular side with specialized human endothelial cells. The Vanderbilt team found that the endothelial cells orient themselves parallel to the direction of flow—a dynamic that had been missing from previous models.

After a few days, when the endothelial cells have attached themselves to the membrane, the scientists flip the device and inject other human cell types that form the barrier—astrocytes and pericytes that wrap around the endothelial cells, and excitatory neurons that regulate the barrier. These cell types all go into the brain chamber, while the porous membrane allows these new cells to make physical and chemical contact with the endothelial cells (similarly to how they would in the blood-brain barrier).

Putting the NVU to the Test

Researchers subjected the NVU to a series of tests; tests that include establishing cell viability and stability over a prolonged time period, as well as effectively generating mature, tight junctions, critical for making the BBB selectively permeable, The NVU device has sailed through each test easily, leading to the next phase of investigation: using it to test drugs and compounds, while providing a dynamic view of how the brain and the blood-brain barrier respond to systemic inflammation.

What’s next? Commercialization! This technology has been patented but is now available for commercialization and larger studies!

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