Achieving a better understanding of how the blood-brain barrier works

Mario Modena is a postdoc working in the Bio Engineering Laboratory at ETH Zurich. If he were to explain his research on the blood-brain barrier – the wall that protects our central nervous system from harmful substances in the blood stream – to an 11-year-old, he would say: “This wall is important, because it stops the bad guys from getting into the brain.” If the brain is damaged or sick, he says, holes can appear in the wall. Sometimes, such holes can actually be useful, for example, for supplying the brain with urgently needed medicine. “So what we are trying to understand is how to maintain this wall, break through it and repair it again.”

This wall is also important from a medical perspective, because many diseases of the central nervous system are linked to an injury to the blood-brain barrier. To discover how this barrier works, scientists often conduct experiments on live animals. In addition to such experiments being relatively expensive, animal cells may provide only part of the picture of what is going on in a human body. Moreover, there are some critics, who question the basic validity of animal testing. An alternative is to base experiments on human cells that have been cultivated in the laboratory.

Cell-cell communication largely overlooked

The problem with many in-vitro models is that they recreate the blood-brain barrier in a relatively simplified way using blood-vessel-wall cells (endothelial cells). This approach fails to represent the complex structure of the human system and disregards, for instance, the communication between the various cell types. Furthermore, many of these models are static. In other words, the cells are floating  in a suspension that is not moving, which implies that fluid flow or the shear stress the cells are exposed to in the body are not considered.

There are also dynamic in-vitro models that simulate flow conditions in the body, but the catch here is that the pumps they require make the experimental setup rather complicated. Alongside all these challenges, there is the problem of measurement: it is all but impossible to take high-resolution images of structural changes to the blood-brain barrier in real time while also measuring the barrier’s electrical resistance, both of which reflect barrier compactness and tightness.

Working under Andreas Hierlemann, Modena and his colleagues spent three and a half years developing the open-microfluidic 3D blood-brain barrier model.

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