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To study disease, scientists grow brain cells from human subjects in rats

Scientists transplanted human brain cells into baby rats’ brains. The cells grew and made connections.

It is part of an effort that aims to better understand brain development and diseases affecting these most complex organs. This makes us who we are, but has been long shrouded in mystery.

Dr. Sergiu Paasca, the senior author of the study that described the findings, said, “Many disorders like autism and schizophrenia may be uniquely human.” However, “the human brain certainly has not been very accessible,” he said.

These are the “promising avenues” to try and tackle these conditions.

This research builds on the previous work of the team creating brain “organoids,” tiny structures that resemble human organs. They have also been made to resemble other organs such as livers and kidneys or key parts.

Stanford University scientists used human skin cells to create stem cells, which were then transformed into different types of brain cells. These cells were then multiplied to create organoids that resemble the cerebral cortex, which is the outermost layer of the brain and plays a crucial role in memory, thinking, reasoning, and emotions.

Scientists implanted the organoids in rat pups at 2 to 3 days of age, when brain connections are still developing. They occupied about a third of the brains of the rats where they were placed. The organoids created working connections between neurons and circuits in the brain.

Although human neurons have been successfully transplanted into rodents in the past, it was usually done in adult animals such as mice. Pasca, a Stanford School of Medicine psychiatry professor, stated that this is the first time organoids have been implanted into early rat brains. This creates “the most advanced human brain circuitry ever constructed from human skin cells” and shows how human neurons can be used to influence animal behavior.

Scientists transplanted organoids in rats’ brains from two sides to demonstrate the practicality of this method. One was from healthy cells, and the other was from Timothy syndrome cells. This rare genetic condition is associated with autism spectrum disorder and heart problems.

They saw the effects of the disease on the activity of their neurons five to six months later. There were significant differences in electrical activity between the two sides. The neurons of the Timothy patient had smaller neurons and didn’t grow as many extensions from input from nearby neurons.

The National Institutes of Health partially funded the study. Researchers said organoids from cells of patients with autism and schizophrenia could be used to replicate the experiments. This could allow them to learn more about the brain’s effects.

Yale University’s Dr. Flora Vaccarino, who had previously grown lumps containing cerebral cortex and DNA from autistic people, said that the study advances the field.

“It’s amazing what they do here in regards to what these cells could show us in terms of their advanced development…in the rat,” stated Vaccarino who was not involved in the study.

Ethics are at stake when experiments on animals are done. Pascal stated that he and his colleagues are aware of the rats’ health and whether they behave normally with the organoids in their bodies. He says they do. Pascal doesn’t believe that this should be done in primates. Ethicists are also curious about the possibility that brain organoids could one day be able to attain human consciousness. Experts say this is highly unlikely.

Scientists are now studying the brain organoids of humans outside of animals. Researchers at ETH Zurich, Switzerland, published a Nature study earlier this month. It described how they grow brain-like tissue in the laboratory and then map the cells in different brain regions and the genes that regulate their development. These structures are being used by some to study autism.

Pascal suggested that brain organoids could be used to test treatments for neuropsychiatric disorders. This is the leading cause of disability in the world. He said that such research could help scientists make progress that was extremely difficult up until now due to the difficulty of getting at the brain. This is “the reason we’re so far behind in psychiatry in terms of therapeutics.”

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