Stem Cells Morph Into Blood-Brain Barrier

For the first time, researchers have coaxed human stem cells to transform into crucial components of the blood-brain barrier (BBB), a defensive wall that protects the brain from blood-borne invaders such as bacteria (Nat. Biotechnol., DOI: 10.1038/nbt.2247). Mats of the tightly packed cells mimic the BBB in humans, the research team says, so they could be used in the future to screen neurological drug candidates.

Starting with stem cells, scientists have previously grown endothelial cells, which typically line the inside of blood vessels. But researchers have never before generated endothelial cells that behave like those in the BBB, says Eric V. Shusta, one of the team leaders and a chemical engineer at the University of Wisconsin, Madison. Like the cells in a human’s BBB, these new petri-dish-derived cells pack together extremely tightly and are studded with specific energy-burning proteins that pump molecules in and out of cells.

To produce the new cells, Shusta says the team first grew stem cells in a culture medium that doesn’t specifically generate any one cell type. That way, he explains, both nerve cells and endothelial cells develop side by side.

“Because both cell types are present, you have an embryonic-brain-like environment,” Shusta adds. The endothelial cells can pick up molecular cues emitted by nearby nerve cells and accordingly develop BBB properties, he says. Eventually, the researchers purified the desired endothelial cells by plating them onto an adherent protein matrix.

Before this stem cell transformation technique becomes a standard laboratory tool, further work is needed, says Babette B. Weksler, a hematologist at Weill Cornell Medical College. “But this imaginative concept will move forward many aspects of brain research.”

One research area that excites Shusta is drug development. The BBB blocks pathogens from accessing the brain but can also lock out helpful therapeutics.

It’s slow going to test drugs’ ability to cross the BBB with cells extracted from animal brains, Shusta says. “But one vial of stem cells can easily be expanded to make tens of thousands of filters for screening chemical libraries.”