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Brain & Nervous System Health Center

Scientists Grow 'Model Brain' From Stem Cells

The tiny 'organoids' have many of the same tissues as nine-week-old fetal brains
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By studying the gene expression of the different tissues of the organoid, researchers were able to identify discrete brain areas including the dorsal cortex, prefrontal cortex, the forebrain and ventral forebrain, the hippocampus, choroid plexus and immature retina -- the beginnings of the eye.

Not all of these areas developed in every organoid, however, and they didn't look exactly like the brains of human embryos as they grow in the womb.

"In a developing embryo, you have the cerebral cortex at the front, then the ventral forebrain below that, and behind that you have the mid-brain, the cerebellum and the brain stem," explained Madeline Lancaster, a postdoctoral researcher at the Institute of Molecular Biotechnology.

"In ours, we don't have that spatial organization. We have those regions, but they're not spatially organized in that manner," she said.

And while researchers found some evidence that the different brain regions were functioning, they don't think the organoids were fully wired and connected the way mature adult brains are, because that kind of connection is something that happens at later developmental stages.

"It's sort of like manufacturing all the transistors and resistors in a radio, but not actually wiring it all up so you can listen to the radio," said Amy Bernard, director of structured science for the Allen Institute for Brain Science in Seattle. "But certainly getting those building blocks set in is the first step."

However, "it's very impressive to see the level of differentiation that's achieved in this model," added Bernard, who was not involved with the study.

To further prove the value of watching early brain development this way, the researchers took stem cells from an individual with microcephaly, a developmental problem that affects about 25,000 of the roughly 4 million children born in the United States each year.

They treated the stem cells with chemicals to return them to an embryonic state and then watched them as they began to grow into an early brain.

Compared to the way previous organoids had grown, the stem cells from the individual with microcephaly stopped dividing earlier, so they had fewer total stem cells with which to build a brain, resulting in a smaller overall brain size.

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