Blood-Brain Barrier Built on a Chip

Vanderbilt-led team developed ‘brain on a chip’

 

A $2.1M “microbrain” challenge for the purpose of studying chemical reactions in the brain was announced in July, 2014. The research grant was awarded to researchers from Vanderbilt University, Vanderbilt University Medical Center, the Cleveland Clinic and Meharry Medical College. According to Vanderbilt, the grant was one of 17 issued “by the National Center for Advancing Translational Sciences at the National Institutes of Health as part of a $70 million ‘Tissue Chip for Drug Testing’ program. The five-year program is a cooperative effort on the part of NIH, the Defense Advanced Research Projects Agency and the FDA.”

[caption id="attachment_2723" align="aligncenter" width="679"] Photo: Courtesy of Vanderbilt University. Top = Brain Cells, Bottom = Bioengineered Vessels. Membrane Between = Blood-Brain Barrier.[/caption]

Why is the blood-brain barrier an important challenge? 

The are many “organs-on-a-chip”  being microfabricated  (see this list called Meet Chip through National Institutes of Health) in order to speed up and improve the pace of research and development particularly for drugs, which are currently tested with cell cultures and animals or humans. The intention is to reduce the time, cost, and technical difficulty of drug development including rapid detection of side effects or lack of effectivity. In addition, it can aid in the understanding of diet and disease in similar ways.

The brain has been historically a challenge for developing drugs or medical therapies because it is surrounded by three highly selective semipermeable membrane barriers that separate blood from brain extracellular fluid (ECF). These barriers block molecules. According to ABC Science: “About 98 per cent of today’s medications cannot cross the blood-brain barrier in significant quantities. Mind you, drugs such as most antipsychotics, sleeping aids and antidepressants are smaller than 500 daltons and can sneak through. But they’re in the two per cent of drugs that can get through.”

How was the Neuro Vascular Unit (NVU) On -A-Chip built? 

The official name of the device is NeuroVascular Unit (NVU) on a chip. The top of the chip is the brain simulation created from stem cells (IPSC’s) to generate the simulated tissues (i.e. brain) and the bottom side simulates blood vessels. The microfluid system transports liquid across the membrane using micropumps that can sample and deliver chemicals/fluids including cerebral spinal fluid. Human endothelial cells line up along the “blood side” in a matter of days and mimic the blood-brain barrier. Cells are also added to the “brain side” to mimic that end of the blood-brain barrier including astrocytes, pericytes, and excitatory neurons.

 

[caption id="attachment_2724" align="aligncenter" width="679"] Photo: Courtesy of Vanderbilt University. Blue Dye = Brain Cells, Red Dye = Blood Circulation[/caption]

According to Research News @ Vanderbilt University: 

https://news.vanderbilt.edu/2012/07/24/microbrain/

“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,” said John Wikswo, the Gordon A. Cain University Professor and director of the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE), who is orchestrating the multidisciplinary effort.

“Wikswo and his collaborators argue that this new type of brain model should provide new 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, as well as uncovering the potential adverse effects of experimental drugs.”

[caption id="attachment_2727" align="aligncenter" width="679"]Photo: Courtesy of Vanderbilt University Photo: Courtesy of Vanderbilt University[/caption]

Related News: 

  1. Vanderbilt UniversityVanderbilt-led team to develop ‘microbrain’ to improve drug testing
  2. NIHBlood-Brain Barrier on a Chip 
  3. Medgadget. Scientists Build Blood-Brain Barrier On-a-Chip to Help Develop Neuro Drugs, Understand Brain Diseases

 

[caption id="attachment_2725" align="aligncenter" width="678"] Gif: Courtesty of mediagiphy.com[/caption]

– Keri Kukral, @kerikukral

 

Video: Courtesy of YouTube, Vanderbilt University 

 

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