WASHINGTON—Tiny, rolling balls of brain cells knocking around in a lab may one day help keep you from losing your marbles—among other things.
The small cellular balls act like mini-brains, mimicking aspects of the real thing, including forming noggin-like structures and pulsing with electrical signals like a thinking mind, researchers reported Friday at the annual meeting of the American Association for the Advancement of Science in Washington. The mini-brains, which can be personalized based on whose cells they’re made from, may soon help scientists study a wide variety of diseases and health problems—from autism and Parkinson’s to multiple sclerosis and Alzheimer’s, as well as stroke, brain trauma, and infections, such as Zika virus.
“There are a variety of places where a mini brain could be useful,” said Wayne Drevets of Janssen Pharmaceuticals Inc., who was not involved with the research. In some cases, they may offer a cheaper, more ethical, and more realistic model for human health than mice and other animals, he and other researchers said at the conference.
Researchers who developed the wee noodles, led by Thomas Hartung, of Johns Hopkins University Bloomberg School of Public Health, hope to have the mini-brains commercially available this year.
But, Hartung admits, “we are not the first or the fanciest.” Other miniature brains have already been made that are more complex and brain-shaped rather than spherical. Yet those tiny brains can be difficult to create and work with, Hartung says. Some require embryonic stem cells to make, which are tricky to get and ethically murky to use. And some of the miniature brains take months to grow and are relatively large (~5 millimeters), which means that they quickly rot from the inside out because they lack blood vessels and circulation to feed the cells imbedded deep in the artificial organ.
Hartung and colleagues came up with a solution to all of those problems. The researchers started off with easy-to-collect adult skin cells and chemically coaxed them to revert to stem cells, nixing the need for embryonic versions. From there, the researchers cajoled the cells into differentiating into a variety of brain cells, including different nerve cells plus glial cells, which support and protect nerve cells.
To get the cells to form teeny brain balls, the researchers put the cells in a shaking incubator where the cells literally roll into small spheres around 350 micrometers in diameter—roughly about three times the thickness of a dollar bill. The tiny size allows the brains to slip past the problem of rotting innards, but they still maintain a brain-like set up with different types of neurons linking up and passing signals. The whole process takes just eight weeks and can produce thousands of mini-brains at once.
On closer examination, the researchers found that many of the nerve cells in the mini-brains developed electrical insulating layers—myelin sheaths—which are made by glial cells and critical for properly functioning nerve cells. Demyelination is a key feature of many neurodegenerative diseases, such as multiple sclerosis (MS). “This promises to be a fantastic model to study MS,” Hartung said.
And the mini-brains spontaneously generated electrical activity, producing brain waves. “They are thinking,” Hartung said—although without any sensory information input, “they have nothing to think about,” he added.
There are countless possibilities of how these brains could help research, Hartung said. In particular, he told Ars that he’s most excited to use the mini-brains to study autism and has already made mini-brains from cells from a person with Down Syndrome. He’s also hopeful that the brains will be useful for pharmaceutical companies testing potential new drugs—offering a more realistic model for how drugs work in people without the need to use animals. After all, Hartung said, humans aren’t 150-pound rats.
But, right now, he cautions, “I’m selling hopes,” as the mini-brains are brand new and haven’t proven useful yet. Still, many researchers at the conference were equally enthused about their potential. After presenting at the meeting, Hartung is now in talks to use the brains to study Zika. The virus, currently exploding throughout South and Central America, has been linked to neurological conditions (some involving demyelination) and a birth defect called microcephaly, in which babies are born with abnormally small and malformed brains.
Others saw potential for the brains to help with development and psychiatry research. Wilson Compton a drug addiction researcher at the National Institutes of Health hopes the brains could help understand how specific brain regions re-wire in addiction. Overall, he said, the brains are a “promising development.”