October 07, 2015

Making 25 cent mini-brains with spheres of nervous system tissue

Brown University researchers describe a relatively accessible method for making a working – though not thinking – sphere of central nervous system tissue. The advance could provide an inexpensive and easy-to-make 3-D testbed for biomedical research.

If you need a working miniature brain — say for drug testing, to test neural tissue transplants, or to experiment with how stem cells work — a new paper describes how to build one with what the Brown University authors say is relative ease and low expense. The little balls of brain aren’t performing any cogitation, but they produce electrical signals and form their own neural connections — synapses — making them readily producible testbeds for neuroscience research, the authors said.


A bundle of neurons
A bioengineering team at Brown University can grow “mini-brains” of neurons and supporting cells that form networks and are electrically active.
Image: Hoffman-Kim lab/Brown University


Tissue Engineering Part C: Methods - Three-Dimensional Neural Spheroid Culture: An In Vitro Model for Cortical Studies


Just a small sample of living tissue from a single rodent can make thousands of mini-brains, the researchers said. The recipe involves isolating and concentrating the desired cells with some centrifuge steps and using that refined sample to seed the cell culture in medium in an agarose spherical mold.

The mini-brains, about a third of a millimeter in diameter, are not the first or the most sophisticated working cell cultures of a central nervous system, the researchers acknowledged, but they require fewer steps to make and they use more readily available materials.

“The materials are easy to get and the mini-brains are simple to make,” said co-lead author Yu-Ting Dingle, who earned her Ph.D. at Brown in May 2015. She compared them to retail 3-D printers which have proliferated in recent years, bringing that once-rare technology to more of a mass market. “We could allow all kinds of labs to do this research.”

The spheres of brain tissue begin to form within a day after the cultures are seeded and have formed complex 3-D neural networks within two to three weeks, the paper shows.

25-cent mini-brains

There are fixed costs, of course, but an approximate cost for each new mini-brain is on the order of $0.25, said study senior author Diane Hoffman-Kim, associate professor of molecular pharmacology, physiology and biotechnology and associate professor of engineering at Brown.

“We knew it was a relatively high-throughput system, but even we were surprised at the low cost per mini-brain when we computed it,” Hoffman-Kim said.

Hoffman-Kim’s lab collaborated with fellow biologists and bioengineers at Brown — faculty colleagues Julie Kauer, Jeffrey Morgan, and Eric Darling are all co-authors — to build the mini-brains. She wanted to develop a testbed for her lab’s basic biomedical research. She was interested, for example, in developing a model to test aspects of neural cell transplantation, as has been proposed to treat Parkinson’s disease. Boutin was interested in building working 3-D cell cultures to study how adult neural stem cells develop.

SOURCES - Brown University, Tissue Engineering Part C: Methods

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