The scientists transplanted human brain cells into the brains of baby rats, where the cells grew and formed connections.
It’s part of an effort to better study the development of the human brain and the diseases affecting this most complex organ, which makes us who we are, but which has long been shrouded in mystery.
“Many disorders such as autism and schizophrenia are probably uniquely human,” but “the human brain certainly hasn’t been very accessible,” said Dr. Sergiu Pasca, lead author of a study describing the work, published Wednesday in the journal Nature.
Approaches that don’t involve harvesting human brain tissue are “promising avenues for trying to tackle these conditions.”
The research is based on the knowledge of the team previous work creating brain ‘organoids’, tiny structures resembling human organs that have also been engineered to represent others such as the liver, kidneys, prostate or key parts thereof.
To make the brain organoids, scientists at Stanford University transformed human skin cells into stem cells and then induced them to become several types of brain cells. These cells then multiplied to form organoids resembling the cerebral cortex, the outermost layer of the human brain, which plays a key role in things like memory, thought, learning, reasoning and emotions.
The scientists transplanted these organoids into 2- to 3-day-old pups, a stage when brain connections are still forming. The organoids grew so that they eventually occupied a third of the hemisphere of the rat’s brain where they were implanted. The organoid neurons have formed functional connections with the circuits of the brain.
Human neurons have been transplanted into rodents before, but usually into adult animals, usually mice. Pasca, a professor of psychiatry at the Stanford School of Medicine, said this was the first time these organoids had been placed in early rat brains, creating “the most advanced human brain circuitry ever built from skin cells.” human and a demonstration that implanted human neurons can influence an animal’s behavior.
To examine a practical use of this approach, the scientists transplanted organoids into both sides of a rat’s brain: one generated from the cells of a healthy person and the other from the cells of a rat. a person with Timothy Syndrome, a rare genetic condition associated with heart problems and the autism spectrum. disorder.
Five to six months later, they saw disease effects related to neuron activity. There were differences in electrical activity on both sides, and the neurons in the person with Timothy syndrome were much smaller and did not grow as many extensions that pick up input from neighboring neurons.
The researchers, whose study was funded in part by the National Institutes of Health, said they could do the same kinds of experiments using organoids made from the cells of people with disorders such as autism or schizophrenia – and potentially learn new things about how these conditions affect the brain too.
Dr Flora Vaccarino of Yale University – who previously cultured pieces containing cerebral cortex made with DNA from people with autism – said the study is pushing the field forward.
“It’s extremely impressive what they’re doing here in terms of what these cells can actually show us in terms of advanced development…in rats,” said Vaccarino, who was not involved in the study. .
Such animal experiments raise ethical concerns. For example, Pasca said that he and his team were aware of the welfare of the rats and whether they still behaved normally with the organoids inside them, which he says they did. Still, Pasca doesn’t believe it should be tried in primates. Ethicists also speculate on the possibility of brain organoids reaching something like human consciousness in the future, which experts say is extremely unlikely at present.
Some scientists study human brain organoids outside of animals. For example, researchers from ETH Zurich in Switzerland published a study in nature earlier this month describing how they grow brain-like tissue from stem cells in the lab, then map the types of cells in various regions of the brain and the genes regulating their development. Some use these structures to study autism.
Pasca said the brain organoids could also be used to test new treatments for neuropsychiatric disorders, the leading cause of disability worldwide. Such research, he said, should help scientists make progress that has been extremely difficult so far because it is so difficult to reach the human brain – which is “the reason why we are so far behind in psychiatry compared to any other branch of medicine in terms of therapeutics.
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