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.”
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.
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.”