A team of scientists at Brown University in Rhone Island have created mini-brains from 3D neural cell cultures and found those cell clusters developed a rudimentary circulatory system.
The team’s tissue cultures of nervous system cells – comprising around 8,000 cell spheres – started to develop a network of non-neural tissue on or around day 3 of the culture. Around two thirds of the cell cultures developed networks of non-neural tissue resembling spaghetti.
To view the blood vessels, the researchers used a range of imaging, staining and fluorescence techniques to determine the structure of the new tissues and how they interact with neural cells. Using a scanning electron microscope, the team was able to show that the new tissues were hollow tubes which would be capable of circulating blood, while their analyses showed that the tubes were comprised of cells and proteins found in blood vessels.
No blood was present in the tubes because the cells were grown in an agarose well plate, although the researchers believe that it would be possible to connect the blood vessels to a microfluidic apparatus that could provide fluid to send through the capillary network. In contrast to the capillary network in a real brain, the mini-brains had far fewer blood vessels and they only lasted for around a week or two, although that would be long enough to take advantage of the vasculature.
Researchers have been using 3D neural cell cultures to create mini-brains in vitro for some time, although in contrast to real brains, these 3D neural cell cultures do not have a vascular system. For a true mini-brain to be created it would be necessary to have at least a basic circulatory system. Only then would it be possible to mimic and study the interactions between neural cells and the circulatory system.
That would be essential for 3D neural cell cultures to be used to study strokes or concussion, and incredibly valuable for studies of Alzheimer’s disease. In the case of the latter, the brain often attempts to repair and even redesign its vasculature to compensate for changes caused by the disease. If this could be mimicked in vitro it would open up many new possibilities for study.
For instance, during the time that the blood vessels are present, researchers could send fluid through the capillaries that contain drugs, or provides oxygen or glucose. By altering concentrations of oxygen, glucose, and pharmaceutical compounds it would be possible to directly monitor their effects on the cells and even mimic what happens with diseases.
Diane Hoffman-Kim, Ph.D., lead author of the study said “We can study a range of injury conditions, several drugs that are being tested, and several conditions, such as stroke and diabetes, together.”
The study – A Three-Dimensional Neural Spheroid Model for Capillary-Like Network Formation – has recently been published in the Journal of Neuroscience Methods.