In a pioneering breakthrough, American neuroscientists have successfully adapted mice to have functioning human cells inside their own brains, with the hope that potential treatments for psychiatric and neurodevelopmental diseases that only occur in humans can now be tested on the laboratory rodents, reports BBC.
While mice with brains that are partly human might sound like a Kafkaesque experiment, the scientists said these “are not mice that think like humans”.
The animals are genetically engineered, and surgically altered, so that some of their brain tissue is human.
The scientists said their work, published in the journal Nature, was carried out with independent ethical scrutiny.
The aim of this ethically complicated breakthrough was to better understand the biology of brain disorders for which there are currently no effective treatments.
Some conditions cannot be studied in a mouse, simply because rodents do not develop some of the brain disorders that we do.
Lead researcher Professor Sergiu Pașca from Stanford University said psychiatry has one of the lowest success rates for clinical trials.
“Even drugs that actually make it to clinical trial – that seem to be working really well in animal models – fail dramatically in clinic,” he said. “That tells us we’re missing a lot of information about human biology, and capturing that will be essential.”
The Stanford researchers said that for some complex conditions, including epilepsy, autism and cerebral palsy, it has the potential to be “transformative”.
“Here we have a new model that allows us to actually capture aspects of human brain function in a way that has not been possible before,” added Pasca.
Mice without their ‘grey matter’
The human brain is made up of billions of cells, interconnected in millions of circuits, making it difficult to understand its development and what exactly is happening – at the cellular level – when things go wrong.
While this research is not the first time human neurons have been implanted in laboratory rodents, these scientists took that approach to a new level.
First, they genetically-engineered mice to develop almost none of their own cerebral cortex – or the outer layer of the brain sometimes referred to as “grey matter”. It handles higher-level thinking, memory and senses.
They then used skin cells taken from humans and reprogrammed them, so they grew into pieces of brain-like tissue. These are structures called organoids – they are not whole brains grown in dishes, more collections of connected, living cells.
When these organoids were implanted into the mouse brain, the cells divided and organised themselves into the animal’s existing brain circuitry, connecting with the rest of the rodent’s brain and spinal cord.
The cortex of the implanted mice is not perfect – normal cortex forms organised, structured layers. And as neuroscientist Dr Ilary Allodi put it, scans of these human-mouse brains look “a bit messy”.
After a few months though, the human cells started to look and function like the outer layer of the mouse’s brain.
About six months after the surgery, scientists put the mice through some basic behavioural tests, observing them as they moved around a small table-top arena.
Pașca said they performed “largely as [the normal] mice did”.
“They don’t have any enhancement,” he added.
Dr Sarah Chan, a reader in bioethics at the University of Edinburgh who was not involved in this research, told BBC News there was “no indication that what’s being created here are mice that can think like humans, or a human brain in a mouse body”.
“But the study prompts us to think about what it might mean when we start changing animal cognition.
“How can we know what it’s like to be one of these mice? And how do we take account of that in the ways that we treat laboratory animals?” she added.
‘A human programme in a mouse environment’
Prof James Ainge, a neuroscientist at St Andrews University, said that while the development was technically very impressive, these mice could be “of limited use”.
This, he said, was partly due to the “ethical issues of raising living human brain tissue in a mouse and what that would mean for the experience of the animal”.
Study details
Developmental xenocortication using human-derived organoids in mice
Konstantin Kaganovsky, Kevin Kelley, Tilo Gschwind et al.
Published in Nature on 16 September 2026
Abstract
The inaccessibility of human brain tissue limits the study of human development and function, a challenge that human stem-cell-derived neural models are beginning to address1,2. Transplantation of neural organoids into rodent hosts enables the in vivo study of aspects of human neurodevelopment and circuit function, alongside behavioural phenotyping of the host animals. However, spatial limitations and competition with host circuits constrain the integration of neural organoids, which is critical for studying disease. Here we establish a transplantation platform using a genetic strategy to effectively deplete glutamatergic neurons from mouse neocortex and hippocampus (apallial) and neonatally engraft the cortical cavity with human stem-cell-derived cortical organoids (hCO) to generate xenocortical mice. This leads to robust graft growth with hCOs occupying most of the cortical volume and generating a diversity of human cortical cell types, including layer 5 extratelencephalic projection neurons. Human cortical neurons integrate with the mouse nervous system, and in vivo cortical graft-wide calcium imaging and electrophysiological analyses revealed patterns of organized activity resembling developing circuits. Behavioural analyses of apallial and xenocortical mice revealed broadly preserved locomotion alongside selective differences in limb coordination and altered organization of spontaneous behaviour. Lastly, this platform enabled behavioural readouts in a model of injury to developing human cortical cells. We envision that xenocortication will be useful for obtaining circuit- and behaviour-level readouts using human neurons to study neurodevelopment, model disease and develop therapeutics.
Nature article – Developmental xenocortication using human-derived organoids in mice (Open access)
BBC News article – Part-human part-mouse brain developed in science breakthrough (Open access)