For the first time ever, researchers have coaxed both embryonic and induced pluripotent stem cells to form the endothelial cells of the blood-brain barrier—an advance that may unlock some of the most closely guarded secrets of this virtually impenetrable wall.
The blood-brain barrier, which separates circulating blood from the fluid that bathes the brain, depends on the unique qualities of endothelial cells, the cells that make up the lining of blood vessels. In many parts of the body, these cells are spaced so that substances can pass through. But in the capillaries that lead to the brain, endothelial cells nestle tightly, creating a semi-permeable barrier that allows essential nutrients and metabolites into the brain while keeping pathogens, harmful chemicals—and many theraputic drugs—locked out.
The new cells exhibit both the active and passive regulatory qualities of those cells that make up the capillaries of the intact brain.
The use of induced cells, which can come from patients with specific neurological conditions, may be especially important for modeling disorders that compromise the blood-brain barrier. Additionally, because the cells can be mass-produced, they could be used to devise high-throughput screens for molecules that may have therapeutic value for neurological conditions or to identify existing drugs that may have neurotoxic qualities. They also could help developmental biologists learn more about how the barrier co-develops with the brain, because neurons develop at the same time as the endothelial cells.
The team, including Chemical and Biological Engineering Professor Eric Shusta (center), Professor Sean Palecek (right), Ethan S. Lippmann (left; now a postdoctoral fellow at the Wisconsin Institute for Discovery) and Samira M. Azarin (now a postdoctoral fellow at Northwestern University), published its findings in the June 24, 2012, edition of the journal Nature Biotechnology. The National Institutes of Health and the National Science Foundation supported the research.