Human brain cells transplanted in rats to study autism, schizophrenia

It’s unbelievably hard to study how these conditions develop. Animals do not experience it as people do and humans simply cannot be researched.

Scientists are able to assemble small sections of human brain tissue made from stem cells in Petri dishes and have already done so with more than a dozen brain regions.

But in dishes, “neurons do not grow to the size that a human neuron in a real human brain would grow,” said Sergiu Pasca. The lead author of the study and Professor of Psychiatry & Behavioural Sciences at Stanford University.

And isolated from a body, they can’t tell us which symptoms a defect is going to cause.

To overcome these limitations, researchers implanted groups of human brain cells, called organoids, in the brains of young rats.

The age of rats was important: human neurons have already been implanted in adult rats, but an animal’s brain stops growing at a certain age, which limits the integration of well-implanted cells.

‘By transplanting them in these early stages, we found that these organoids can become relatively large, they become vascularised (receive nutrients) by the rat, and can cover about one-third of the hemisphere of a rat (brain),’ said Pasca.

Blue light ‘reward’

To check if human neurons fit properly into the brain and body of rats, the air was blown through the animal whiskers, causing electrical activity in human neurons.

This revealed an entrance connection — external stimulation of the rat’s body was treated by the human tissue in the brain.

Scientists then tried the opposite: could human neurons send signals to the rat’s body?

They implanted human brain cells engineered to react to blue light and then trained the rats to expect a “reward” from the water of a beak when the blue light shines on the neurons via a cable into the skulls of the animals.

After two weeks, the impulse of blue light sent the rats rushing towards the pouring beak, according to research published on Wednesday in the journal Nature.

The team now uses this technique to show that organized with Timothy syndrome patients develop more slowly and display less electrical activity than those healthy people.

Tara Spires-Jones, professor at the British Dementia Research Institute at the University of Edinburgh says the work “has the potential to further what we know about human brain development and neuro-developmental disorders”.

But she noted that human neurons “have not reproduced all the important characteristics of the developing human brain” and more research is needed to ensure the technique is a “robust model”.

Ethical debates

Spires-Jones, who was not involved in the research, also highlighted potential ethical issues, “including if these rats will have a more human thought and consciousness”.

Pasca stated that careful observations of rats suggest that brain implants have not changed them, or caused pain.

‘There is no impairment of rat behaviour or rat welfare… there is no augmentation of functions,” he said.

He argued that the limitations on how human neurons integrate into the rat’s brain provide “natural barriers” that prevent the animal from becoming too human.

Rat brains develop much faster than humans, “so there is a limit to what the rat cortex can integrate,” he said.

But in species closer to man, those barriers may no longer exist, and Pasca said he would not support the use of the technique in primates at this time.

He believes, however, that there is a “moral imperative” to find ways to better investigate and treat psychiatric disorders.

‘Surely the more human these models become, the more uncomfortable we feel,’ he said.

But ‘human psychiatric disorders are largely human. So we’ll have to think very carefully…. how far we want to go with some of those patterns.