Designing In Vitro Models of the Blood-Brain Barrier

Choosing the right model, be it 3-D or 2-D, requires wading through varied cell sources, cell types, and cell culture conditions.

Written byJyoti Madhusoodanan
| 7 min read

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© JACOPIN/BSIP/SCIENCE PHOTO LIBRARYA molecular force field protects the human brain. Aided by support cells such as astrocytes and pericytes, endothelial cells lining brain capillaries produce junction-forming proteins to create a barricade with a high electrical resistance, as well as a range of transporters and receptor proteins that keep molecules in the blood from crossing into the brain. This blood-brain barrier protects the brain and spinal cord from infections, toxins, and inflammation—but also blocks drugs from reaching injured or dysfunctional neurons, hampering efforts to treat brain injury or disease.

Since the early 1970s, researchers have tried to mimic this protective layer of cells in vitro, first attempting to isolate intact brain capillaries, and, later, working to isolate and culture endothelial cells from animal tissue in single-layer sheets. Such static, two-dimensional cultures are still widely used, particularly in screening new drug molecules. As cell culture techniques have advanced in the last decade, however, more-sophisticated models that better reflect the structure’s physiological roles have begun to emerge. Some rely on human stem cells, while others incorporate multiple cell types, often from different animal sources, grown together in various arrangements. Microfluidic models with a variety of 3-D structures are also gaining in popularity as systems in which to study the functions of a range of cell types ...

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