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The Power of Mini-Brains

By Julie Scharper
Thomas Hartung is an environmental health scientist, molecular microbiologist, and immunologist at the Johns Hopkins Bloomberg School of Public Health.

The spheres are tiny, no bigger than the eye of a fly. Yet they are complex—a tangle of nerve cells beginning to sort themselves into specialized roles. And scientists around the world believe they could reveal the mysteries of the brain while reducing the need for lab rats. These spheres, called “mini-brains,” can be created from the cells of any person. Researchers take a small piece of skin and then transform it into stem cells, without using fetal tissue. Scientists then induce these stem cells to reproduce and to become nerve cells.

“Mini-brains allow you to see how neurons interact with each other,” says Thomas Hartung, an environmental health scientist, molecular microbiologist, and immunologist at the Johns Hopkins Bloomberg School of Public Health. “We can listen to how electrical signals in the brain are being produced and propagated.”

Hartung, who also directs the school’s Center for Alternatives to Animal Testing, believes that mini-brains could eliminate the use of hundreds of thousands of lab rats. Mini-brains are not only cheaper and easier to maintain than rats, they also more accurately reflect the human nervous system, Hartung says.

“While rodent models are useful, we’re not 150-pound rats,” Hartung says. Since the mini-brains are composed of human cells, they allow researchers to see how different factors influence human neurons.

While scientists around the world have been experimenting with mini-brains in recent years, Hartung’s team is the first to create an easily reproducible brain organoid, or a three-dimensional cluster of cells that mimics some of the characteristics of an organ. Hartung’s team can produce thousands of identical balls of cells, freeze them, and ship them to a lab for immediate use. Hartung hopes to provide other organoids, such as mini-stomachs or small intestines, to researchers as well.

Hartung believes the mini-brains will provide insight on autism, Alzheimer’s, and multiple sclerosis, among other conditions. Mini-brains are already helping researchers better understand the devastating effects of the Zika virus. A husband-and-wife research team in the Johns Hopkins School of Medicine’s Institute for Cell Engineering has been studying the Zika virus on different types of mini-brains. Neuroscientist Guo-li Ming and her husband, fellow neuroscientist Hongjun Song, have been examining the mosquito-borne virus—which causes babies to be born with microcephaly. By using the mini-brains, they’ve been able to discern that the virus appears to infect the specialized stem cells that form the outer layer of the brain. Next, they hope to test drugs on the mini-brains to see if they could arrest the harmful effects of Zika.

Hartung believes that the proliferation of mini-brains will lead to many such advances. His mini-brains take about 10 weeks to develop and resemble the brains of developing fetuses. (The cells have begun to form different types of neurons, although distinct brain structures have not yet emerged.) The balls of cells are immersed in a perpetually swirling liquid, causing them to form a sphere.

While the mini-brains are remarkable tools for understanding the brain, they do not actually think, Hartung says. The neurons spontaneously communicate with each other, sending electrical impulses from one cell to the next.

“There’s no input and no output. There’s no learning,” says Hartung. “They have nothing to think about.”

Image above by Monica Ramos; Image on left by Tyler Charlton

Grown in a lab, mini-brains allow researchers to see how neurons interact, and they have the potential to provide insight on autism and Alzheimer’s, among other conditions.

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