【Nature】Stanford University implants "mini human brains" into mice, creating a new era of organoid research!

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Written by Sophia

Scientists want to use tiny brain-like structures grown from human stem cells, brain organoids, to study neurodegenerative and neuropsychiatric diseases
in human development.
But so far, organoids have only mimicked the human brain
.
They don't develop blood vessels, so they don't get nutrients, which means they don't thrive for long
.
And they don't get the nutrients they need to grow adequately: In the brains of human infants, the growth of neurons and the development of connections with other neurons come in part from sensory input
.

A recent study suggests that miniature human brain structures transplanted into mice can send signals and respond to
environmental cues picked up by rats' whiskers.
This demonstration that neurons grown from human stem cells can interact with nerve cells from living rodents, potentially leading to a way to
test therapies for diseases in the human brain.
The study was published in the journal Nature
.

style="box-sizing: border-box;" _msthash="251139" _msttexthash="322530">Major discoveries

 01 

To provide this stimulation and support to brain organoids, Sergiu Pasca, a neuroscientist at Stanford University in California, and his colleagues grew these structures from human stem cells and then injected them into the brains of newborn young mice, expecting the human cells to grow as the mice's own cells grow
.
The team placed organoids in a brain region called the somatosensory cerebral cortex, which receives signals from rat whiskers and other sensory organs and then relays them to other brain regions
that interpret the signals.

Human brain cells mature much more slowly than rat cells, so the researchers had to wait more than six months for the organoids to fully integrate into the rat brain
.
But when they examined the animals' brains at the end of that time, they found that the integration was so successful that it was almost like adding "another transistor"
to the circuit.

Paola Arlotta enthuses: "This is an important step for organoids to tell us about the more complex nature of the brain, although transplantation procedures may still be too expensive and complex to be a standard research tool
.
" Arlotta adds, "The next step will be to study how individual human neurons, not just fully developed organoids, are integrated into rat
brains.
" ”

Behavior triggers

 02

The researchers describe how they genetically modified neurons in organoids, and the team trained mice to lick their mouths to receive water
when the lights were on.
Later, when the researchers shone light onto the hybrid brain, the mice were prompted to lick their mouths, meaning that the human cells were well integrated enough to help drive some of the animals' behaviors
.
In addition, when the researchers adjusted the mice's whiskers, they found that human cells in the sensory cortex responded, suggesting that these cells were able to pick up sensory information
.

Human neurons generated from stem cells and transplanted into rat brains (right) grew more fully than
neurons grown in a dish (left).

To demonstrate the promise of their work in studying brain diseases, Pasca and his colleagues also created brain organoids from stem cells from three people with Timothy syndrome, a condition that can cause symptoms
similar to autism.
These tiny structures looked identical to any other brain organoid cultured in a petri dish, but when the researchers transplanted them into rats, they didn't grow as big as the others, and their neurons didn't fire
in the same way.

Rusty Gage is excited to see these results
.
In 2018, he and a team of researchers discovered that transplanted human brain organoids could be integrated into the
brains of adult mice.
Mice don't live as long as rats, but the brains of newborn pups are more plastic than those of adult animals because they are better able to receive new cells
.

Ethical challenges

 03 

"We face challenges," Gage said
.
"But I do believe that the transplant program will be a valuable tool
.
"

Some challenges are ethical
.
There are concerns that creating rodent-human hybrids could harm animals, or create animals
with human brains.
Last year, a team organized by the National Academies of Sciences, Engineering, and Medicine released a report concluding that human brain organoids are still too primitive to become conscious, to acquire human-like intelligence or to acquire other abilities
that might require legal regulation.
Pascal said his team's organoid transplants did not cause problems such as seizures or memory loss in rats, and it didn't seem to significantly change the animals' behavior
.

But Alotta, a member of the National Academy of Sciences panel, said problems could arise
as science advances.
We can't just talk about it once, we need to weigh the future medical concerns about human organoids with the needs of
patients with neurological and psychiatric disorders.
Brain organoids and human-animal hybrid brains could shed light on the underlying mechanisms of these diseases and allow researchers to test treatments for
conditions such as schizophrenia and bipolar disorder.

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style="white-space: normal;box-sizing: border-box;" _msthash="251157" _msttexthash="19521346">Note: This article is intended to introduce the progress of medical research and cannot be used as a reference
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.