According to recent study, scientists have implanted human brain cells into the developing rat brains, where the cells have grown and developed connections.
It’s a part of an attempt to better understand how the most complicated organ in the body—the brain—which shapes who we are but has long been cloaked in mystery.
Although “the human brain clearly has not been particularly accessible,” Dr. Sergiu Pasca, senior author of a research explaining the discovery, noted that “many illnesses like autism and schizophrenia are likely uniquely human.”
“Promising paths in attempting to handle these diseases” are methods that don’t entail removing brain tissue.
The study relies on the group’s earlier efforts to create “organoids” that resemble the brain as well as other human organs like the liver, kidneys, and prostate or important portions of them.
Scientists at Stanford University converted human skin cells into stem cells, and then persuaded them to differentiate into several kinds of brain cells to create the brain organoids. These cells then multiplied to create organoids that resembled the cerebral cortex, the outermost layer of the human brain and a crucial component of memory, thought, learning, reasoning, and emotions.
These organoids were inserted into 2- to 3-day-old rat pups, while the brain is still developing its neural connections. The organoids developed to the point that they finally took up a third of the rat’s implanted hemisphere of the brain. Organoid-derived neurons established functional connections with neural circuits in the brain.
Rodents have previously received human neurons by transplantation, mainly in adult mice. This is the first time these organoids have been implanted into young rat brains, according to Pasca, a professor of psychiatry at the Stanford School of Medicine. This process produced “the most advanced human brain circuitry ever built from human skin cells and a demonstration that implanted human neurons can influence an animal’s behavior.”
The Timothy syndrome, a rare genetic condition linked to heart issues and autism spectrum disorder, was studied by scientists who implanted organoids into both sides of a rat’s brain. One of the organoids was made from the cells of a healthy person, and the other from the cells of a person with Timothy syndrome.
They first saw disease-associated effects connected to the activity of the neurons five to six months later. Electrical activity on the two sides was different, and the neurons from the Timothy syndrome patient were significantly smaller and didn’t grow as many extensions that could take up input from neighboring neurons.
The team of researchers said they could conduct the same kinds of experiments using organoids made from the cells of people with disorders like autism or schizophrenia — and possibly learn new things about how these conditions affect the brain as well. The National Institutes of Health contributed to the study’s funding.
The discovery advances the discipline, according to Dr. Flora Vaccarino of Yale University, who previously created lumps of cerebral cortex using DNA from autistic patients.
Vaccarino, who wasn’t involved in the research, said, “It’s incredibly remarkable what they do here in terms of what these cells can truly show us in terms of their advanced growth… in the rat.”
Such animal testing raises ethical questions. For instance, Pasca said that he and his colleagues are aware of the rats’ welfare and if they continue to act normally in the presence of the organoids, which he claims they do. Pasca disagrees that this should be tested on primates, however. Researchers now think it is very implausible for brain organoids to develop anything like to human consciousness, but ethical theorists are interested in the potential.
Outside of animal studies, several scientists are investigating human brain organoids. For instance, researchers from ETH Zurich in Switzerland described how they are developing brain-like tissue from stem cells in the lab and then identifying the cell types in distinct brain areas and genes governing their growth in a report published in Nature earlier this month. These structures are being used by some to research autism.
According to Pasca, brain organoids might be used to evaluate brand-new therapies for neuropsychiatric illnesses, which are the leading cause of disability in the world.
The difficulty of accessing the human brain, he said, is “the reason why we’re so much farther behind in psychiatry compared to any other discipline of medicine in terms of treatments,” and such research, he argued, could enable scientists to achieve breakthroughs that have been incredibly difficult until now.