organoid
It may sound like something out of science fiction, but scientists grew mini-brains in a lab with functional neural networks that can produce brain waves. (Credit: Shutterstock)

These pea-sized lumps of
cells don’t look like much, but they are mini-brains, also called brain
organoids, that were grown in a lab using human stem cells. 

And for the first time,
scientists have created mini-brains with humanlike neural networking capable of
producing brain waves similar to those observed in premature babies. The work comes
from a team of scientists at the University of California in San Diego who had
their research published in Cell Stem Cell on Thursday.

 “We never had a brain
organoid that can function like the human brain,” said biologist and researcher
Alysson Muotri. “The electrical activity of these brain organoids are emitting
something we see during normal human development. So, it’s a strong indication
that what we have should work and function like the human brain.”

These brain organoids are
still a far cry from real brains. But according to Muotri, it’s a step
toward growing a fully formed and functional human brain in the lab. 

Brain organoids could one
day provide scientists with a clearer picture of what’s happening during brain
development. Neurological and psychiatric disorders such as autism, epilepsy,
bipolar disorder, depression, autism and schizophrenia are thought to have
their roots in how our brains develop.

“It’s not ethical to study [an embryonic human brain] during a pregnancy, so we have to rely on other models, mostly animal models, and those are far from the human brain,” Muotri said. “And there’s many neurological conditions that we know happen at these very specific stages. Most of the genes that are implicated in autism have peak of expression, or activity, in the fetal stages, but you only see the consequences of behavior a little later in life.”

These pea-size brain organoids are 10 months old. (Credit: Alysson Muotri)

Making a Mini-Brain

To grow a mini-brain in the
lab, scientists take skin stem cells and reprogram them into pluripotent
stem cells, which can develop into any type of bodily cell or
tissue. From there, researchers place them in a cell
culture that mimics the environment that allows our own brains to
grow. 

“By giving them a nice
environment, the neurons will just thrive and make more synapses and take their
time to mature and form these micro circuitries that the brain requires to have
computational power,” he said. 

Bursts of Brain Activity

Over the course of 10
months, the mini-brains showed consistent increases in brain wave
activity, or electrical signals triggered by firing neurons, similar to
what’s observed in the developing brain.

At two months old, the mini-brains
first began to emit some sparse electrical activity at a single frequency, like
that seen in immature human brains. But by 10 months old, the mini-brains
produced regular brain wave activity across a range of frequencies, similar to
the brains of older fetuses or infants. It suggested that the mini-brain’s
neurons had matured and become interconnected, forming networks. 

Brain Freeze

But, eventually, electrical
activity in the organoids plateaued, as if they were stuck in
infancy.  

“The reason might be that
you need more cells, or the conditions are not ideal,” Muotri said. “Or, it
might be that the human brain, after nine months, requires input. And the input
further develops these networks.”

While more work is needed
to understand how to take organoids to later stages of brain development, the
team may have uncovered something that challenges previous beliefs about human
brain development. The researchers thought fetuses in the womb picked up
on sounds and other sensory information from the outside world that helped
their neural networks to mature. But that wasn’t the case at all for the
organoids. 

 “What we’ve shown is that, no, you can have a
brain outside the uterus, that has no stimulus from the outside, and it
generates this sophisticated network activity … the brain is preprogrammed to
wire that way,” he said.  

Although brain organoids
may behave like human brains in some ways, they’re still far from the real
thing. For instance, they lack nutrient-delivering vascular systems and not all
cell types are represented. 

And, as far as the
scientists know, the organoids aren’t capable of consciousness. But, creating a
mini-brain that’s conscious maybe isn’t as far-fetched as it sounds. Mutori
said the idea of producing an organoid with a neural network seemed impossible
just five years ago. But given what he and his team accomplished, he’s optimistic
that scientists will grow brains that are increasingly humanlike. 

“I think we will learn how
to make different brain regions and stick them together: a human cortex
connected with a human thalamus, together with a hippocampus. By sticking these
pieces together, we may be able to reconstruct circuitries that are important
in learning, for example. And we can then understand how the human brain
learns, processes information and stores memories. I think in the next
five to 10 years, there will be a lot of advances on the frontier.”



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