What happens when human brain cells grow inside a mouse?

Scientists in the United States have grown large amounts of human brain tissue inside mice's brains, potentially offering a new way to study disorders such as autism, epilepsy and cerebral palsy that are difficult to model in animals.

The study was led by neuroscientists at Stanford University and published in Nature yesterday  (16 September), the BBC reported. 

Researchers transplanted human brain organoids into genetically engineered mice that had space created in their brains for the human tissue.

Within two to three months, the human tissue occupied more than 90% of the vacant space. It also sent nerve projections deep into the mice's nervous systems.

The mice did not develop human-like intelligence or thoughts.

Instead, the experiment was designed to give human brain cells a living environment where they could grow, mature and connect with other parts of the nervous system.

Why scientists are using mice

Studying the human brain is difficult. It contains billions of cells that form complex networks controlling movement, memory, senses and other functions.

Scientists can grow human brain organoids in laboratories using human stem cells. These small, three-dimensional structures can reproduce some features of human brain development.

But organoids grown in laboratory dishes have limitations.

They do not have the full network of blood vessels, sensory signals and connections found in a living body.

Researchers have therefore been trying to grow human brain tissue inside animals.

Earlier work by the Stanford team showed that human brain organoids could be transplanted into newborn rats. The human cells matured and connected with parts of the animals' nervous systems.

The latest study takes that approach further.

Mice with space for human brain tissue

The researchers first genetically engineered mice so that neurons that would normally form much of the neocortex and hippocampus did not develop.

The neocortex is the outer part of the brain involved in functions such as perception, memory and complex processing.

This created space for the transplanted human tissue.

The scientists then reprogrammed human skin cells and turned them into brain-like tissue called organoids.

These organoids were transplanted into the developing mouse brains.

With less mouse brain tissue competing for space, the human cells grew rapidly.

Within two to three months, they occupied more than 90% of the vacant space and sent nerve projections into the mice's nervous systems.

The human tissue did not simply remain as a lump.

It developed into different types of neurons, including specialised human and primate brain cells that are not normally found in mice.

The researchers also found cells resembling von Economo neurons. These cells are associated with social cognition and have been linked to some neurodegenerative diseases.

Not mice that think like humans

The presence of human brain tissue raises an obvious question: could the mice develop human-like thoughts or abilities?

The researchers found no evidence of that.

Behavioural tests showed that the mice retained broadly normal movement. However, the researchers also observed some differences in limb coordination and spontaneous behaviour.

The timing of the transplant was also important.

The procedure was carried out after the basic wiring of the mouse brain had already begun to form. This reduced the possibility that the human cells could take over complex brain functions, according to Nature.

Dr Sarah Chan, a bioethicist at the University of Edinburgh who was not involved in the study, told BBC News that there was no indication the experiment had produced mice capable of thinking like humans.

But she said the research raises broader ethical questions.

As researchers alter animal cognition, it becomes harder to know what the animals might experience. This also raises questions about how they should be treated in laboratories, she told BBC News.

A human brain programme inside a mouse

The human cells also behaved in ways that surprised researchers.

Dr Ilary Allodi, a neuroscientist at the University of St Andrews who was not involved in the study, told BBC News that some human and primate-specific cell types developed naturally inside the mice.

She described the process as keeping a "human programme" inside a mouse environment.

The mouse, in effect, provides a living environment for the human tissue to grow and mature.

This could be important for studying diseases that involve complex interactions between different types of brain cells.

Human brain disorders are often difficult to reproduce in mice. Some conditions simply do not occur naturally in rodents.

This is one reason why promising treatments can fail when they move from animal studies to human clinical trials.

Sergiu Pașca, one of the study's researchers, said psychiatry has one of the lowest success rates for clinical trials. He argued that researchers need better models of human biology before testing potential treatments.

The new mice could provide one such model.

A new way to study brain disorders

The researchers believe the model could eventually be used to study several neurological and neurodevelopmental conditions.

These include epilepsy, autism and cerebral palsy.

The potential value is not that the mice become more human.

It is that human brain cells can now be studied inside a living nervous system.

This gives researchers access to signals and connections that cannot be fully reproduced in a laboratory dish.

It could also help scientists study how human brain cells respond to potential treatments.

However, the approach has limitations.

Prof James Ainge, a neuroscientist at the University of St Andrews who was not involved in the research, said the mice could have limited practical use.

He also pointed to ethical questions surrounding the growth of human brain tissue inside animals.

The researchers said the work underwent independent ethical scrutiny and that the animals were raised under strict welfare guidelines.

The ethical question remains

The science may be striking, but the ethical questions remain.

The central concern is not whether a mouse can suddenly become human.

It is whether adding human brain tissue could change an animal's experiences in ways that scientists cannot fully measure.

For now, the researchers' behavioural tests have not shown evidence of human-like cognition.

That distinction is important.

These are not miniature humans with mouse bodies. They are laboratory animals with human-derived neural tissue integrated into their brains.

The experiment instead opens another route for studying the human brain.

Researchers have human cells, animal models, and computer simulations. They also have brain organoids that can reproduce parts of human brain development.

Now, they have another possibility: human brain tissue developing inside a living animal.

As Allodi told BBC News, scientists studying human brain disease have long worked with mice, cells grown on plates and neural networks on computers.

This new approach adds another option.

The real test will be whether it can help researchers better understand human brain disorders and develop treatments that work in people.