Building a better blood-brain barrier model

"Our model takes a new approach to mimic the blood-brain barrier outside of a living system. These miniature spheroids are relatively straightforward to culture, and yet it is able to reproduce many of the key blood-brain barrier properties and functions," said lead author Choi-Fong Cho, PhD, of the Department of Neurosurgery. "Our hope is that these findings will further advance neuroscience research and expedite the discovery and design of brain-penetrant drugs to treat diseases of the brain and central nervous system."

Current models of the blood-brain barrier rely largely on either animal models -- which are expensive, laborious and can only be used to test a limited number of compounds at a time -- or cells grown in the lab. For the latter, it's very difficult to replicate the conditions found in the human body. Cells are often grown on flat plastic surfaces, isolated by cell type, and may become less and less like the unique cells found in the brain over time. The new technique grows different kinds of brain cells -- endothelial cells, pericytes and astrocytes -- together, allowing them to spontaneously form multicellular spheroids. These self-assembled structures closely resemble the blood-brain barrier organization and can be used to predict drug penetration capabilities -- molecules that can penetrate the surface of the spheres and accumulate inside are more likely to be able to penetrate the blood-brain barrier and enter the brain in a living organism.

The research team performed several tests on these spheroids to establish some of the key properties of the blood-brain barrier that allow it to restrict the influx of foreign molecules. The spheroid model scored much better on many of these properties than the standard model in use today. The team also used the spheroids to identify new brain-penetrant molecules, which could hold high potential for delivering therapeutics across the blood-brain barrier.

"We plan to use this model going forward in our own research to identify new therapeutics for glioblastoma," said senior author Sean Lawler, PhD, of the Department of Neurosurgery. "This is a very versatile model and should allow our group and others to test not only molecules but also viruses, cells and more that may be able to cross the blood-brain barrier."