Blood vessels found in the brain play an important role in maintaining what is known as the blood-brain barrier (BBB), a structural and chemical barrier between the brain and the circulatory system. One of the roles of the BBB is to protect the brain from harmful toxins, but this protective measure makes it challenging for treatments for neurological diseases or brain injury to be effectively delivered to the brain. Therefore, there is a lot of interest in better understanding the structure and function of the BBB and its contribution to disease.
To study this “gatekeeper to the brain” in a human-relevant fashion, researchers at the Wyss Institute at Harvard University, led by Dr. Donald Ingber, developed a simplified three-dimensional in vitro model of the BBB “on-a-chip.”
Essentially, they created a small channel within a polymer chip and filled this with a gel matrix combined with a particular cell type known to be important for the function and maintenance of the BBB. Next, they hollowed out an opening within the center to create the shape of a blood vessel, and then introduced two other cell types important for the function of the BBB. The cells self-assembled and assumed 3-D positions similar to what would be observed in vivo.
Researchers tested this model to see how it would respond to signals known to induce inflammation, an important component of many neurological disorders, including Alzheimer’s disease and stroke. Cells in the model produced neuroprotective proteins and responded to inflammation in ways that “more closely mimicked those observed in the living brain” than cells grown using more traditional tissue culture approaches.
This model offers improvements over existing in vitro approaches, while enabling important human-relevant research on the BBB to take place without relying on animal models. It has a number of potential applications, ranging from its use in studies examining inflammation to understanding how and why different drugs can pass through the BBB. It may ultimately aid in the development of more effective therapies. Future work will also include expanding on this model and integrating additional cell types to create more sophisticated and complex cultures.
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Crossing a barrier in the study of neurological disease
A team at the Wyss Institute for Biologically Inspired Engineering, led by Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., has advanced the Institute’s Human Organs-on-Chips technology by developing a method for modeling the 3D structure of the human blood-brain barrier inside a microfluidic device, which will help scientists study human neurovascular function and inflammation in vitro.
For more information see: Wyss Institute