GoKawiilHuman brain tissue transplanted into mice that lack a key part of their brains can grow to occupy most of the vacant space and wire into the animals’ nervous systems.
That’s according to a study published on 16 September in Nature1, which describes the most extensive integration of human brain cells into an animal so far. The experimental strategy overcomes hurdles that have long stymied researchers studying neuropsychiatric illness in laboratory-grown brain tissue.
Human brain cells implanted in rats prompt excitement — and concern
The hybrid animals offer an unprecedented way to test drugs and study diseases that involve abnormal brain development such as cerebral palsy, says study co-author Sergiu Pașca, a neuroscientist at Stanford University in California. “We now have a very powerful new system” for understanding “what makes the human brain unique and uniquely susceptible to disease”, he says.
Although creating human–mouse hybrids, or chimeras, can cause discomfort and raise ethical questions for some people, researchers working in this field say that precautions are taken with investigations such as this one. For instance, the work underwent extensive oversight, including review by independent bioethics panels, according to Pașca.
The timing of the procedure — carried out days after the mouse pups’ birth, past the point at which the brain’s core wiring is already in place — also ensures that human cells cannot take over complex thinking, says Madeline Lancaster, a developmental neurobiologist at the University of Cambridge, UK, who was not involved in the study. In fact, behavioural tests revealed that the human tissue did not enhance the rodents’ intellect.
“The goal here is clearly not to make a mouse that’s super intelligent — nor would it be,” she says. The goal here is to have human brain tissue inside a realistic body setting “so you can start using it to understand human neurobiology and human neurological diseases”.
Implant impacts
Neuroscientists have grappled for decades with their inability to study living human brain tissue. Although human brain organoids, which are clusters of neurons grown from human stem cells in Petri dishes, have offered a window into early neurodevelopment, they generally lack blood vessels and do not have a body to send and receive signals from.
In 2022, Pașca and his colleagues showed2 that transplanting human brain organoids into newborn rats allowed the structures’ neurons to mature and wire into sensory pathways. Two years later, the group used those rats to evaluate how effective drugs called antisense oligonucleotides were against Timothy syndrome, a severe genetic condition linked to autism and epilepsy3.
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