Researchers at the KTH Royal Institute of Technology in Stockholm, Sweden, engineered a blood-brain barrier on a chip using human-derived stem cells. The device closely mimics the blood-brain barrier and allows the researchers to study its function and the effect of drugs without having to use experimental animals. By incorporating sensors, the chip can monitor barrier function in near real time.
The blood-brain barrier is a layer of endothelium that lines the vessels of the brain, and prevents the ingress of various small molecules. This layer protects the brain from many substances in the blood that could otherwise cause damage or problems in this highly specialized organ. Drugs intended to treat neurological issues in the brain must be able to cross the barrier. Moreover, the barrier can be affected and somewhat compromised by various physiological processes, including inflammation, but it has been difficult to study these phenomena.
This latest technology provides welcome assistance for researchers who hope to unravel the mysteries of the blood-brain barrier. The research group behind the development has created a blood-brain barrier on a chip, using human-derived stem cells to form the barrier.
“We successfully based the barrier on human stem cell-derived cells so this model is relevant to drugs being tested for humans, while other models are made with animal cells or are too simple to monitor closely,” said Isabelle Matthiesen, a researcher involved in the study.
The device provides near continuous monitoring of barrier integrity, allowing researchers to study processes that can affect the barrier in neurodegenerative diseases, such as inflammation. The current research group used the device to study the effect of inflammation on barrier integrity and the effect of anti-inflammatory drugs on this process. Electronic sensors within the device provide a read-out of barrier integrity approximately once a minute.
“As an example, when you first administer a drug, it causes a huge change in cells, then levels out,” said Thomas Winkler, another researcher involved in the study. “In the typical methods of testing drugs, you wouldn’t see those rapid changes. We can now see that the breakdown of the blood brain barrier happens fast under stress and we could see how that could be prevented with the anti-oxidant.”
Study in journal Small: Continuous Monitoring Reveals Protective Effects of N-Acetylcysteine Amide on an Isogenic Microphysiological Model of the Neurovascular Unit