A new study shows that laboratory-grown miniature models of the wrinkled surface of the human brain can be used to repair injuries in the brains of living rats, thereby repairing broken connections in rodents’ sensory processing systems. One day, such mini-brains — known as brain organoids — could potentially also be used to repair the brains of human patients, the study authors suggest.
“I see this as the first step in developing a new strategy to repair the disease Brain,” called dr Han Chiao Isaac Chen (opens in new tab)senior author of the study and assistant professor of neurosurgery at the University of Pennsylvania Perelman School of Medicine.
Finally, organoids could be used to restore brain function after traumatic injury, invasive surgery, or strokeor to combat the effects of neurodegenerative diseases such as Parkinson’s, Chen told Live Science. However, we are still many years away from applying the technology to humans, he said.
In their new study, published in the journal on Thursday (Feb. 2). cell stem cell (opens in new tab)Chen and his colleagues showed that brain organoids grew from humans stem cells can be transplanted into the visual cortex of an injured rat, where information from the eyes is first sent for processing.
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When light hits the retina in the eye, an electrical message is sent to the “primary” visual cortex, which begins analyzing the basic characteristics of what’s in front of the eye. This data is then passed to the “secondary” visual cortex, which takes the analysis one step further. In the new study, adult rats suffered a severe injury to the secondary visual cortex, and the researchers essentially used an organoid to plug the resulting hole in the brain.
In previous research, scientists transplanted single brain cells into healthy rodents of various ages and organoids into the brains of very young, uninjured rodents; By transplanting organoids into older, injured rats, this study signals another step toward using organoids to repair brain injuries, Chen said.
The team grew their organoids from a type of human stem cell, which can give rise to many different types of cells. For 80 days, the researchers had used chemical cues to coax these stem cells into 3D clumps containing many, but not all, of the cell types found in the human cerebral cortex, the brain’s wrinkled outer layer. The cortex contains six distinct layers of tissue, and by day 80, the organoids grown in the lab bore similar but somewhat rudimentary layers.
“This structure is really very important in defining how the brain actually works,” Chen said of the 3D architecture of the organoids. Although the clumps of tissue resemble real cortex in many ways, “they are by no means perfect,” he added.
To transplant each organoid into a rat brain, the team removed a piece of each rodent’s skull, placed the organoid inside and sealed the hole with a protective cap. The rats were given immunosuppressive drugs during and after the procedure to prevent their bodies from rejecting the transplant.
Over the following three months, the rats were blood vessels infiltrated the organoids, and in turn, the cells of the organoids became physically intertwined with the rest of the rodent’s visual processing systems.
The organoids grew slightly larger during this time, gained new cells, and lengthened wires to connect to the rats’ brain cells. The researchers mapped these new connections with a fluorescent tracer, which showed that the organoids had successfully connected to the retina via this network of wires. In addition, the researchers showed the rats visual stimuli – including flashing lights and black and white bars on a screen – and found that their organoids activated in response, as would be expected from an intact visual cortex.
The team did not perform any visual or behavioral tests on the rats to study how their vision changed after their injuries or transplant procedures. The researchers are now working on such evaluations. In the future, they plan to test whether organoids can be similarly integrated into other parts of the brain, such as the motor cortex, which controls movement, and investigate what factors control the speed and extent of this integration.
In addition, the team hopes to improve brain organoids to better mimic a real human brain. “We want a substrate that more faithfully replicates what the brain looks like,” as it should theoretically make the organoids more useful for future brain repair, Chen said.