Pea-Brained

ILLUSTRATION BY DAVID PLUNKERT

 

Take a millionth of a human brain, and squeeze it into a chamber the size of a mustard seed.

Next, link it to a second chamber filled with cerebral spinal fluid, and thread both of them with artificial blood vessels to create a microenvironment that makes brain cells behave as if they were in a living brain. Then surround the chambers with a battery of sensors that monitors how cells respond when exposed to minute quantities of dietary toxins, disease organisms, or new drugs under development.

Creating such a “microbrain bioreactor” is the aim of a new $2.1 million research grant awarded to an interdisciplinary team of researchers from Vanderbilt, the Cleveland Clinic and Meharry Medical College. The grant is one of 17 that are part of a $70 million “Tissue Chip for Drug Testing” program by the National Center for Advancing Translational Sciences at the National Institutes of Health.

Microfabricating organ simulators containing small populations of human cells is known as organ-on-a-chip technology. The idea behind it is to bridge formidable gaps between the tools researchers currently use to develop new drugs—cell cultures and animal and human testing. These gaps add substantially to the difficulty and expense of developing new drugs and contribute to the large number of experimental drugs that aren’t effective or have unacceptable side effects when they are finally tested on people.

The brain is a tough target for drug development because it is surrounded by three barriers that protect it from intruders. Most formidable of these is the blood-brain barrier (BBB). It surrounds blood vessels that service the brain, allowing passage of compounds the brain needs but blocking passage of other types of molecules. Additional barriers protect neurons from contaminants in the cerebral spinal fluid and protect cerebral spinal fluid from contaminants in the blood. Not only do these barriers block potentially harmful molecules, but neuroscientists also have discovered that they occasionally alter the chemistry of some of the compounds they let through.

“Given the differences in cellular biology in the brains of rodents and humans, development of a brain model that contains neurons and all three barriers between blood, brain and cerebral spinal fluid, using entirely human cells, will represent a fundamental advance in and of itself,” says John Wikswo, the Gordon A. Cain University Professor and director of the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE). Wikswo is orchestrating the multidisciplinary effort.

This new type of brain model, argue Wikswo and his collaborators, should provide insights into how the brain receives, modifies and is affected by drugs and disease agents. By replicating the forms of chemical communication and molecular trafficking that take place in the human brain, the device will allow them to test the effectiveness of various drug and nutritional therapies designed to prevent both acute injuries like strokes and chronic diseases like obesity and epilepsy, and to uncover potential adverse effects of experimental drugs.