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Salk Researchers Work Toward Growing More Realistic 3D Mini-Brains

A tiny three-dimensional model of the human brain is seen in this fluorescent...

Credit: Madeline Lancaster/MRC-LMB (Medical Research Council, Laboratory of Molecular Biology), UK

Above: A tiny three-dimensional model of the human brain is seen in this fluorescent cross-section, Dec. 20, 2016.

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The hope is that one day, researchers could use these tiny models of the human brain to better understand how disorders like schizophrenia and autism take root during early brain development.

In a new study published Tuesday, scientists at the Salk Institute detail new work toward creating more realistic 3D "mini-brains," tiny models of the human brain that researchers are already using to better understand threats like the Zika virus.

A few years ago, scientists showed it was possible to build three dimensional brain tissue in the lab using stem cells. Those stem cells can even be derived from a patient's skin, opening up the possibility of creating mini-brains containing a person's unique DNA.

The hope is that one day, researchers could use these genetically matched mini-brains to better understand how disorders like schizophrenia and autism take root during early human brain development.

But first, scientists need to know how faithfully these mini-brains recreate actual brain function. For the new study, researchers at the Salk Institute teamed up with the European scientists who pioneered this technique to put mini-brains to the test.

They performed genetic analysis on the mini-brains and compared them with actual brain tissue in similar stages of development. The results showed that these tiny models of the human brain were not perfect, but in some ways they were closer to actual brain tissue than the cell cultures used in many labs today.

Salk researcher Chongyuan Luo says the mini-brains recreated important structural features that two-dimensional cell cultures don't.

"These features will be lost when cells are grown in a two-dimensional configuration," he said. "Whereas many of these structural signatures, such as the layer structure of our brain tissue, is being recapitulated in this 3D brain."

Despite their improvements, mini-brains still fell short of fully capturing the epigenetic profile of real brain tissue, Luo says.

"By doing this project, we're hoping to find molecular signatures that can give us an idea on how to further improve the mini-brain system," he said.

Despite their limitations, Salk scientist and senior study author Joseph Ecker notes that mini-brains are already proving to be useful in certain research. Earlier this year, a team at UC San Francisco used 3D mini-brains to forge stronger links between the Zika virus and microcephaly.

Correction: An earlier version of this story mistakenly paraphrased Salk researcher Chongyuan Luo as saying mini-brains were not better than 2D models at capturing the epigenetic profile of real brain tissue. That point has now been clarified.

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