In 2015, scientists at Brown University developed "mini-brains," models of living brains created from 3D cultures of neural cells. Like organs-on-chips, these models could help reduce our reliance on animal testing in the search for new treatments and drugs, and make early results more accurate. Now, the researchers have discovered something new about these mini-brains: the neural cells are growing their own blood vessels too, opening the door for better studies of stroke, Alzheimer's and concussion.
Each measuring less than a millimeter wide, Brown's mini-brains are created thousands at a time, grown from living rat neural cells. They can't think, but the neurons are electrically active, composed of several types of cells and arrange themselves in a natural three-dimensional structure. Serving as reliable models of the real thing, scientists can study how neural cells develop, and what effect injuries or drugs may have, without the need for animal testing.
But neurons are only part of the picture. Brains require blood, and until now, the mini-brains seemed unable to replicate the vascular system that feeds them. But as the researchers continued to work with the models, they noticed that about two thirds of their mini-brains had developed tangles of non-neural tissue, which further study indicated were blood vessels.
"This is exciting because real brains have vasculature," says Diane Hoffman-Kim, senior author of the study. "We rely on it. For our neurons to do their thing, they have to be close to some blood vessels. If we are going to study lab models of the brain, we would love for them to have vasculature, too."
By imaging the mini-brain blood vessels, the researchers were able to identify the cells and proteins as those normally found in blood vessels, and studying a cross-section under a transmission electron microscope revealed that the hollow tubes are structurally up to the task of transporting blood. The system isn't as dense as in a real brain, and they tend to only last one or two weeks, but the finding does improve the mini-brains' usefulness.
With this new avenue of research open, the team has already started using the mini-brains to study the vasculature, starving the models of oxygen or glucose to see how it affects the blood vessels. Future research could also involve hooking the mini-brains up to a microfluidic apparatus to get the metaphorical blood pumping, or study the effects of stroke, Alzheimer's and brain injuries on the vasculature, which is sometimes rewired in real brains in response to these disorders.
"We can study a range of injury conditions, several drugs that are being tested and several conditions — such as stroke and diabetes — together," says Hoffman-Kim.
The research was published in The Journal of Neuroscience Methods and the team demonstrates the finding in the video below.
Source: Brown University
