Scientists transplanted human brain cells into the brains of baby rats, where the cells grew and formed connections.
It is part of an effort to better study the development of the human brain and diseases that affect this most complex of organs, what makes us who we are but has long been shrouded in mystery.
“Many disorders like autism and schizophrenia are probably uniquely human,” but “the human brain certainly wasn’t very accessible,” said Dr. Sergiu Pasca, senior author of a study describing the work, published Wednesday in the journal Nature.
Approaches that do not take tissue from the human brain are “promising ways to address these diseases.”
The research builds on the team’s previous work To create brain “organoids,” tiny structures resembling human organs that were also made to represent others such as the liver, kidneys, prostate or important parts of them.
To create the brain’s organoids, Stanford University scientists converted human skin cells into stem cells and then coaxed them into becoming different types of brain cells. These cells then multiplied and formed organoids that resemble the cerebral cortex, the outermost layer of the human brain that plays key roles in things like memory, thinking, learning, reasoning, and emotions.
Scientists transplanted these organoids into 2- to 3-day-old rat pups, a stage when brain connections are still forming. The organoids grew to eventually occupy a third of the hemisphere of the rat brain where they were implanted. Neurons from the organoids formed working connections with circuits in the brain.
Human neurons have previously been transplanted into rodents, but more commonly into adult animals, usually mice. Pasca, a professor of psychiatry at Stanford School of Medicine, said this is the first time these organoids have been introduced into early rat brains, creating “the most advanced human brain circuitry ever built from human skin cells and a demonstration that implanted human neurons can affect an animal’s behavior.”
To study a practical application of this approach, scientists transplanted organoids into both sides of a rat’s brain: one from cells from a healthy individual and another from cells from a person with Timothy syndrome, a rare genetic disorder linked to heart problems and autism -Spectrum interference.
Five to six months later, they saw effects of the disease related to the activity of the neurons. There were differences in the electrical activity of the two sides, and the neurons of the person with Timothy syndrome were much smaller and didn’t sprout as many processes that pick up input from nearby neurons.
Researchers, whose study was funded in part by the National Institutes of Health, said they could do the same experiments on organoids made from the cells of people with disorders like autism or schizophrenia — and potentially learn new things about how they change Medical conditions affect brain health as well.
dr Flora Vaccarino of Yale University – who previously grew cerebral cortex clumps made with DNA from people with autism – said the study is advancing the field.
“It’s extremely impressive what they’re doing here, what these cells can actually show us in terms of their advanced development…in the rat,” said Vaccarino, who wasn’t involved in the study.
Such animal testing raises ethical concerns. For example, Pasca said that he and his team are aware of the welfare of the rats and whether they are still behaving normally with the organoids inside them, which he thinks they are doing. However, Pasca doesn’t think this should be attempted in primates. Ethicists also wonder about the possibility of brain organoids achieving anything like human consciousness in the future, which experts say is extremely unlikely at this time.
Some scientists are studying human brain organoids outside of animals. For example, researchers from ETH Zurich in Switzerland published a study in Nature Earlier this month they described how they grow brain-like tissue from stem cells in the laboratory and then map the cell types in different brain regions and genes that regulate their development. Some use these structures to study autism.
Pasca said brain organoids could also be used to test new treatments for neuropsychiatric disorders, which are the leading cause of disability worldwide. Such research, he said, should help scientists make advances that have hitherto been extremely difficult because the human brain is so hard to get at — that’s “that’s why we’re so much more behind in psychiatry than in any.” other branch of psychiatry medicine in therapeutic terms.”
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