The blood-brain barrier is one of the greatest challenges that modern medicine has to overcome if we want to be able to fight neurological diseases using drugs. Animal models serve a purpose, but they’re not very good at replicating the human blood-brain barrier (BBB) as results often don’t translate during clinical trials. A better way to study the BBB is needed and researchers at Georgia Tech have now developed a chip that accurately replicates its function using the human cells that form this important part of our anatomy.
Astrocyte brain cells are the primary constituent of the BBB, interfacing between the neurons and blood vessels, but having them live and grow outside a living brain has proven difficult. 2D cultures tend to grow astrocytes that are misshapen, but the Georgia Tech team was able to grow these cells in 3D which resulted in them having the star shape they’re named after. Moreover, the model BBB worked more like the real thing, with cultured endothelial cells performing as expected.
“No animal model comes close enough to the intricate function of the human blood-brain barrier. And we need better human models because experimental drugs that have successfully entered animal brains have failed at the human barrier,” said YongTae Kim, one of the study leads.
More details, according to Georgia Tech:
“Upon the brain’s request, astrocytes collaborate with the vasculature in real-time what the brain needs and opens its gates to let in only that bit of water and nutrients. Astrocytes go to get just what the brain needs and don’t let much else in,” Kim said.
Astrocytes form a protein structure called aquaporin-4 in their membranes that are in contact with vasculature to let in and out water molecules, which also contributes to clearing waste from the brain.
“In previous chips, aquaporin-4 expression was not observed. This chip was the first,” Kim said. “This could be important in researching Alzheimer’s disease because aquaporin-4 is important to clearing broken-down junk protein out of the brain.”
“When we purposely confronted the astrocyte with pathological stress in a 3D culture, we got a clearer reaction. In 2D, the ground state was already less healthy, and then the reaction to pathological stresses did not come across so clearly. This difference could make the 3D culture very interesting for pathology studies.”
Study in Nature Communications: Microengineered human blood–brain barrier platform for understanding nanoparticle transport mechanisms
Via: Georgia Tech