Human brain cells implanted in rat brains form connections with their hosts

Scientists have transplanted human brain cells into rat brains, discovering that the new neurons will grow as the rat grows and even help influence their behavior. The research has resounding implications not only for neurological research, but also for the ethics of creating animal-human hybrids in this way.

The Stanford University team took bundles of lab-grown human neurons and all the supporting cells around them and transplanted them into the developing brains of newborn rats. As the rodents grew, the human neurons integrated into the brain and formed working circuits, which the researchers now say they can use to study neurodevelopmental disorders.

“We can now study healthy brain development as well as brain disorders thought to be rooted in development in unprecedented detail without having to remove tissue from a human brain,” said Pasca, Bonnie Uytengsu and Stanford Brain Family Director Organogenesis and co-author of the study, in a statement.

“We can also use this new platform to test new drugs and gene therapies for neuropsychiatric disorders.”

The team used a method they previously described in 2015, where human skin cells are turned into stem cells and then differentiated into various brain organelles. In this way, the lab could create specific areas of the brain in miniature organoid form—not as developed as those in a naturally occurring brain, but perfect for transplanting into an animal model.

Because of the babies’ remarkable ability to make new connections as the brain develops, nearly 100 rat pups just two or three days old received transplants of these bundles of human brain cells into the exact same area of ​​the brain.

It wasn’t long before the rat’s internal machinery started moving into the human cells to supply them with blood and nutrients. Suddenly stocked with immune cells and all the necessary ingredients to thrive, the human neurons grew from just a fraction of an inch to take up about a third of the rat’s hemisphere. Compared to the neurons that remained covered in the Petri dish, these transplanted neurons were now six times larger and significantly more complex.

The researchers then transplanted two different sets of human cells—one from a patient with Timothy syndrome, a neurological disorder linked to autism and epilepsy, and a control group without the syndrome—into the same brain in both hemispheres. In the Timothy syndrome hemisphere, the neurons developed differently and were much smaller, giving researchers unprecedented insight into how these disorders develop.

Continuing with the other rats, the researchers then demonstrated that the human circuit directly affected their behavior by specifically stimulating small organelles within the rats’ brains in a Pavlovian experiment. They also found neither a benefit nor a deficit in the functioning of the rats with the implants, suggesting that they had a role in cognitive function but did not improve it.

“This is the most advanced human brain circuit ever made from human skin cells and a demonstration that implanted human neurons can influence the behavior of an animal,” Pasca said.

“Our platform provides, for the first time, behavioral cues for human cells and could, we hope, accelerate our understanding of complex psychiatric conditions.”

Their research was published in the journal Nature.

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