These cheap balls of neurons are no Einsteins, but they’re perfect for research.
A quarter can buy you some time on a parking meter, a giant gumball from a machine, and not much else—unless you’re in the market for a miniature brain.
For just 25 cents, biomedical engineers at Brown can manufacture, from rodent tissue, a teeny brain—about a third of a millimeter in diameter—that can produce electrical signals and form synapses. It may not be good for thinking (sorry, Scarecrow), but that petite sphere of central nervous system tissue is functional enough to test drugs, neural transplants, or how stem cells work.
“We think of this as a way to have a better in vitro model that can maybe reduce animal use,” says Molly Boutin PhD’17, co-lead author of a paper in Tissue Engineering: Part C in December. “A lot of the work that’s done right now is in two-dimensional culture, but this is an alternative that is much more relevant to the in vivo scenario.” Just a small sample of living rodent tissue can make thousands of minibrains, the authors wrote. They isolate and concentrate the desired cells with a centrifuge and use that to seed the cell culture in medium in an agarose spherical mold. The orbs begin to form within a day after the cultures are seeded and form complex, 3-D neural networks within two to three weeks.
Though the mini-brains aren’t the first or the most sophisticated working cell cultures of a central nervous system, they require fewer steps to make and use more readily available resources. “The materials are easy to get and the mini-brains are simple to make,” co-lead author Yu-Ting Dingle ’06 ScM’07 PhD’15 says. Comparing them to retail 3-D printers, she adds, “We could allow all kinds of labs to do this research.”
Senior author Diane Hoffman-Kim PhD’93, associate professor of medical science and of engineering, says her lab wanted to develop a model to test aspects of neural cell transplantation, as has been proposed to treat Parkinson’s disease. Boutin, who is one of Hoffman-Kim’s graduate students, wants to study how adult neural stem cells develop.
Hoffman-Kim hopes the mini-brains will proliferate to other labs. “We think you shouldn’t have to equip yourself with a microelectronics facility, and you shouldn’t have to do embryonic dissections in order to generate an in vitro model of the brain,” she says.
