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The brain is the only part of the body outfitted with astrocytes, which regulate nourishment uptake and waste removal in their own, unique way.
"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."
One of the study's co-authors, Dr. Allan Levey from Emory University, a highly cited researcher in neurological medicine, is interested in the chip's potential in tackling Alzheimer's. Another, Dr. Tobey McDonald, also of Emory, researches pediatric brain cancer and is interested in the chip's possibilities in studying the delivery of potential brain cancer treatments . Barrier acting healthy
Astrocytes also gave signs that they were healthier in the chip's 3D cultures than in 2D cultures by expressing less of a gene triggered by pathology.
"Astrocytes in 2D culture expressed significantly higher levels of LCN2 than those in 3D. When we cultured in 3D, it was only about one fourth as much," Kim said.
The healthier state also made astrocytes better able to show an immune reaction.
"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." Nanoparticle delivery
In testing related to drug delivery, nanoparticles moved through the blood-brain-barrier after engaging endothelial cell receptors, which caused these cells to engulf the particles then transport them to what would be inside the human brain in a natural setting. This is part of how endothelial cells worked better when connected to astrocytes cultured in 3D.
"When we inhibited the receptor, the majority of nanoparticles wouldn't make it in. That kind of test would not work in animal models because of cross-species inaccuracies between animals and humans," Kim said. "This was an example of how this new chip can let you study the human blood-brain barrier for potential drug delivery the way you can't in animal models." Source:
Georgia Institute of Technology Journal reference:
Ahn, S.I., et al. (2020) Microengineered human blood–brain barrier platform for understanding nanoparticle transport mechanisms. Nature Communications . doi.org/10.1038/s41467-019-13896-7 .
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