Scientists transplanted human cells into a rat’s brain to create “hybrid circuits”

Scientists at the Stanford School of Medicine have successfully implanted human brain cells into the brains of rats. As the cells grew and connected to form “hybrid circuits,” the rats’ brains developed as expected. The purpose of this experiment was to create new approaches to studying the development of the brain and mental diseases. According to a news release, scientists will be able to study the impact it has on animal behaviour by growing and modifying human brain tissue inside a rat’s brain.

Scientists will be able to conduct studies that would be too intrusive, challenging, and occasionally just impossible to do on humans thanks to this “living laboratory” of a rat’s brain, they added.

Without having to remove tissue from a human brain, scientists can now examine both normal brain development and brain illnesses that are believed to have their origins in development in unprecedented detail. The corresponding author of the study that was published in the journal Nature, Sergiu Pasca, said in a news release that we may also use this new platform to test novel medications and gene therapies for neuropsychiatric illnesses. At the Stanford School of Medicine, Pasca teaches psychiatry and behavioural sciences.

In order to conduct this investigation, stem cells were first created from human skin cells. The stem cells were directed to differentiate into a variety of distinct brain-cell types in a lab setting to create an “organoid” that mimics the cerebral cortex, the most recent component of the brain and its outermost layer.

“We’ve been making ever more complicated circuits in a dish using organoids and sophisticated combinations of them, called assembloids. But neurons within these lab dishes are still lagging in their development compared with what you’d see in a naturally developing human brain,” Pasca said.

These assembloids were cultured for two months before being implanted into young rats’ brains when they were between two and three days old. In humans, this period corresponds to infancy. It was crucial to employ newborn rats rather than adult ones since the brain is significantly more resistant to creating new connections as it matures. Brain connections are created early in development.

Over 100 rats underwent this transplant during the study, with the organoids being positioned in the same area of each rat’s brain to provide easy monitoring. The rat’s cells quickly spread into human tissue. Rat endothelial cells entered the brain implants and formed blood vessels, feeding the human cells with nutrition and signalling agents. Or they “moved right in,” as Pasca put it.

The next step was to determine whether these organoids would truly be useful in identifying the origins of human neuropsychiatric diseases now that transplantation had been successful. The researchers selected Timothy syndrome, a genetic condition that has a substantial association with autism and epilepsy, for their study. They used skin cells from a Timothy syndrome patient to make an organoid that was then grafted into the rat’s brain on one side.

They implanted an organoid made from a healthy person’s cells on a matching area on the other side to act as a control. The researchers were able to clearly distinguish between the electrical activity on both sides after five to six months.

Fewer dendrites, or brush-like extensions that serve as an antenna for information from neighbouring regions, emerged from the Timothy syndrome neurons, which were considerably smaller.

This shows that implanted human neurons can affect an animal’s behaviour and is the most sophisticated human brain circuitry ever created from human skin cells. Our approach, which we believe will help us better comprehend complicated mental diseases, offers behavioural readouts for human cells for the first time.

To better understand how mental illnesses such as schizophrenia and autism influence the brain, Pasca thinks that comparable comparisons can be done utilising cells from individuals who have these conditions.