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Chip Device Simulates Blood-Brain Barrier

Brain circuits

(NIH.gov)

13 June 2019. A bioengineering lab developed a miniaturized chip with living cells that offers a realistic simulation of the blood-brain barrier to test new drugs. Researchers from the Wyss Institute for Biologically Inspired Engineering at Harvard University and University of Wisconsin in Madison describe their microfluidics, or lab-on-a-chip device in today’s issue of the journal Nature Communications.

The blood-brain barrier acts as a safety measure to protect the brain from foreign substances crossing from the blood stream while allowing nutrients to flow through. Blood vessels in the brain form a support network for brain functions, with tightly-packed cells lining blood vessels. This barrier also keeps out drugs to treat neurological conditions, such as Parkinson’s or Alzheimer’s disease, and its impaired functioning is also implicated in these disorders. So far, no efficient method is available to penetrate this barrier, preventing some 98 percent of current drugs from reaching the brain or central nervous system.

Studying actions of drugs in the brain are hampered further by the lack of realistic animal models. Brain anatomy in most small lab animals, such as mice, differs markedly from humans. And attempts so far to simulate the blood-brain barrier, including at the Wyss Institute and partner labs, have not yet simulated all of the functions performed by the blood-brain barrier. In August 2018, as reported in Science & Enterprise, the Wyss Institute devised a simplified blood-brain barrier that links together the various functions on 3 different chips.

The Wyss Institute-Wisconsin team created its new blood-brain barrier chip starting with induced pluripotent stem cells, also known as adult stem cells derived from existing tissue cells rather than embryos. The researchers transformed these stem cells into brain microvascular endothelial cells, the cells found in fine blood vessels in the brain. In addition, the team performed this transformation under low-oxygen conditions, similar to those in the brain.

The researchers then transferred these lab-grown brain cells into the Wyss Institute’s earlier blood-brain barrier chip using channels lined with astrocyte cells that support the signaling functions of neurons and and pericytes that regulate the flow of substances across the endothelial cells, a key part of the blood-brain barrier. Tests of the chip show it functions much like the blood-brain barrier, or BBB, blocking transport proteins called efflux pumps that promote toxic substances, while encouraging some peptides and antibodies to cross the barrier.

“Our approach to modeling drug and antibody shuttling across the human BBB in vitro” says Donald Ingber, director of the Wyss Institute and senior author of the paper in a Wyss Institute statement, “with such high and unprecedented fidelity presents a significant advance over existing capabilities in this enormously challenging research area.”

Wyss Institute recently started its Brain Targeting Program to build on the results of this project for identifying proteins that interact with human endothelial cells in fine blood vessels found in the brain and other organs. The institute says it’s collaborating with multiple pharmaceutical companies in this program and will make the technologies available on a non-exclusive basis.

Ingber is also a founder of the company Emulate Inc. that develops and commercializes organ-simulating chips, and chairs Emulate’s scientific advisory board.

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