Stem cells may provide answer to blood-brain barrier

Madison, Wis. - The blood-brain barrier is a big problem when it comes to getting drugs into the brain, and researchers at the University of Wisconsin-Madison believe they have found a way to address the problem by using stem cells.

The findings are the result of a collaborative study funded with a grant from the National Institutes of Health and
led by UW-Madison professor of chemical and biological engineering Eric V. Shusta, who described the experiment in a recent online edition of the Journal of Neurochemistry.

For this study, researchers used neural stem cells derived from the fetal brains of rats, and co-cultured them along with blood-brain barrier cells - endothelial cells that make up the blood-brain barrier. They found that the stem cells could have a profound effect on sealing the blood-brain barrier, which happens very early in development.

Although the blood-brain barrier protects the brain from chemicals and other harmful agents, it also has frustrated neuroscientists and drug companies because it restricts the administration of drugs.

As Shusta explained, the blood-brain barrier "dictates traffic in and out of the brain." Teaming up

Shusta's research team also includes UW-Madison School of Medicine and Public Health professor and stem cell authority Clive Svendsen, and UW-Madison doctoral fellow Christian Weidenfeller.

In essense, they have demonstrated that developing brain cells can release factors that might coax small blood vessels to exhibit the properties of the blood-brain barrier. Svendsen believes the finding could produce insights into how drugs could overcome the barrier and treat disease.

"The idea is that we can use this process to mimic what happens in normal development so that we can make a better model of the blood-brain barrier, and that's important for testing drugs," he said.

Their next move will be to reproduce the findings using human endothelial cells and neural stem cells, which would represent a breakthrough because there is no reliable model for the human blood-brain barrier and because many promising drugs are made up of molecules too big to pass through the human barrier.

Handy stem cells

According to Svendsen, studying the human cells could produce results after a year or more of work, and he noted that researchers at UW-Madison have access to a lot of different types of human stem cells.

"The interactions between the stem cells and endothelial cells hasn't really been explored before," he noted. "It's another area I think where stem cells will come in handy, and having an in vivo model that is really sealed gives you a chance to test whether drugs will get through the blood-brain barrier before giving them to animals or people."

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