Scientists have recently made a wondrous variety of mini-brains -- 3-D cultures of neural cells that model basic properties of living brains -- but a new finding could add to the field's growing excitement in an entirely new "vein": Brown University's mini-brains now grow blood vessels, too.
The networks of capillaries within the little balls of nervous system cells could enable new kinds of large-scale lab investigations into diseases, such as stroke or concussion, where the interaction between the brain and its circulatory system is paramount, said Diane Hoffman-Kim, senior author of the study in The Journal of Neuroscience Methods. More fundamentally, vasculature makes mini-brains more realistic models of natural noggins.
"This is exciting because real brains have vasculature," said Hoffman-Kim, an associate professor of medical science and of engineering at Brown. "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."
Making the most of mini-brains
Especially because scientists can make them by the hundreds, mini-brains hold promise not only for advancing medical and scientific research, but also for doing so with less need for animal models. Hoffman-Kim's lab first described its mini-brain method in 2015. While the engineered tissues appeared relatively simple compared to some others, they were also relatively easy and inexpensive to make.
But what had remained unnoticed at the time, even by the inventors, was that the little 8,000-cell spheres cultured from mouse cells were capable of growing an elementary circulatory system.
Only as members of the lab including lead author and Brown Graduate School alumna Molly Boutin continued to work with and study the mini-brains did they discover that after about day three of culture, about two-thirds of the mini-brains had grown networks of non-neural tissue. Closer inspection revealed that these tangles of spaghetti were self-assembled (i.e. they just grew) tubes made of the cells and proteins found in blood vessels.
The new study features a wide variety of imaging experiments in which staining and fluorescence techniques reveal those different cell types and proteins within the mini-brain spheres. The study also documents their integration with the neural tissues. Cross-sections under a transmission electron microscope, meanwhile, show that the capillaries are indeed hollow tubes that could transport blood.
Of course, there is no blood in a tiny mini-brain, Hoffman-Kim said. They exist in an agarose wellplate, not in a living animal. But she's currently working with a colleague at Brown to design a way to connect the mini-brains with a microfluidic apparatus that could produce an external source of circulation through a mini-brain.
"We've sketched on a few napkins together," she quipped.
The capillary networks are not as dense as they would be in a real brain, she acknowledged. The study also shows that they don't last longer than about a week or two.
Aware of both their constraints and their potential, Hoffman-Kim's lab has already started experiments to take advantage of the presence of vasculature. Study second author Liana Kramer, a Brown senior, has begun looking at what happens to the vasculature and neural cells when mini-brains are deprived of oxygen or glucose. Later that same test bed could be used to examine the difference that different drugs or other treatments make.
Vasculature is particularly important not only because it delivers oxygen, glucose and medicine to brain cells, but also because research shows that in strokes, Alzheimer's disease and brain injury, the brain sometimes attempts to redesign its vasculature to compensate for what's happening to it. The mini-brains could allow researchers to observe such responses amid different lab-created conditions and treatments, Hoffman-Kim said.
"We can study a range of injury conditions, several drugs that are being tested and several conditions -- such as stroke and diabetes -- together," she said.
In addition to Boutin, who is now at the National Institutes of Health (NIH), Hoffman-Kim and Kramer, the paper's other authors are Liane Livi, Tyler Brown and Christopher Moore.
Funding from the National Science Foundation, NIH, Brown University, Brown alumna Donna McGraw Weiss and Jason Weiss, and the Association of Migraine Disorders supported the research.
David Orenstein | EurekAlert!
More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
19.01.2018 | Materials Sciences
19.01.2018 | Health and Medicine
19.01.2018 | Physics and Astronomy