A New Study Casts Doubt on Lab Models of the Blood Brain Barrier

Research by scientists at Cornell University and Weill Cornell centered around the endothelial cells that form a barrier between tissues and vessels. They control the flow of fluid and substances in and out of tissues.

NeuroScience News recently reported details of a critical flaw in blood-brain-barrier lab models.

Endothelial cells have been used for years to create lab models of the human blood-brain barrier (BBB). A significant flaw was discovered when scientists realized that the endothelial cells used in lab studies did not contain several critical proteins that exist in natural endothelial cells.

The endothelial cells that were used in lab studies more closely resembled epithelial cells. Epithelial cells are not usually located in the brain. The study was first published on February 4, 2021, in Proceedings of the National Academy of Sciences.

About the Discovery

Dr. Dritan Agalliu, co-study lead at Columbia, points out that studying the human BBB is challenging in part because of a wide range of differences between the BBB of animals and humans. Dr. Agalliu observed that the newly developed cells were not acting like normal endothelial brain cells.

A More Accurate Model

Dr. Agalliu first noticed that human endothelial cells that were being used in the labs were produced based on a study published study in 2012 that included a form of endothelial cell. Endothelial cells line blood vessels in the brain and in the spinal cord. They develop barriers that preclude the entry of antibodies or dangerous substances entering the bloodstream and finding their way into the brain.

Dr. Agalliu was of the opinion that the process used in the past produced cells with a flawed composition. Researchers at Weill Cornell were of the same opinion and formed an investigative team with Columbia scientists. Their goal was to duplicate the previous protocol and enact RNA sequencing of the cells.

Fortunately, the researchers were able to design a more accurate model of the human BBB and correct the inaccurate lab models to a reasonable extent.

This new discovery will create an improved model and enable scientists to study neurological disorders in order to develop beneficial drugs that can penetrate the BBB.

In addition, the team was able to identify three unique genes that react like actual endothelial cells. But the scientists acknowledge that more research is needed with the goal of creating endothelial cells that they can rely upon to accurately model the BBB. Check out the original study here.