Scientists mak mice wi pairt-human brains

Researchers hae created mice wi hauf-human brains in a bid tae unnerstand and develop new treatments for disorders sic as schizophrenia, epilepsy, cerebral palsy, intellectual disability and rare forms o dementia.

The scientists transplantit lab-grown human brain cells intae animals that wur engineered tae be born withoot a cortex or hippocampus. This made space for the human tissue tae grow inside the rodents' skulls.

The procedure means scientists can nou tak cells frae patients wi brain disorders, turn thaim intae brain tissue in the laboratory, and grow that tissue in livin animals. The animals can syne be studied tae see hou the disorder taks haud in human brain tissue, and hou drugs micht treat the conditions.

“We hae been tryin real hard as a community tae find therapeutic solutions for these conditions, but the reality is that in psychiatry and neurology we hae been left ahint [by] every single branch o medicine and we hae fewer therapeutics than, again, every single branch o medicine,” said Sergiu Pașca, a professor o psychiatry wha led the research at Stanford University.

“That cud be because the human brain is vera complex, but it is also because the human brain is inaccessible,” he addit. “Tae a muckle extent, our goal has been tae mak aspects o human brain development and function accessible for investigation.”

The wark is the latest frae the field o neural organoids, whaur human brain cells, grown in the lab, assemble intae tiny but complex structures that mimic some o the features o real brains.

While potentially transformative for brain medicine, organoids hae sparkit a wave o ethical concerns, no least aboot whether the clumps o tissue cud become conscious or feel pain, and the welfare o animals implantit wi organoids.

Pașca said the wark had received extensive ethical oversight frae the start.

Experts said this wad need tae continue. Emily Jackson, professor o law at London School o Economics and chair o a recent report on neural organoids for the Nuffield Council on Bioethics, said: “Animal welfare is a real important concern, and it will be necessary tae closely monitor these animals in order tae evaluate the impact on thaim.”

In previous wark, the Stanford team transplantit human neurons intae rat brains. The tissue tuik root and wired intae the animals' brain circuits, but there was ower little room for the human tissue tae grow vera muckle.

Tae solve the problem, the researchers genetically engineered mice tae stunt the growth o key brain regions, the cerebral cortex and hippocampus. Surprisingly, the mice survived because the remainin parts o the brain tuik on new roles. While the mice luik normal, they are cautious on their feet and mair forgetfu.

Writin in Nature, Pașca describes hou the mice wur injectit wi human brain organoids that wur theirsels created by reprogrammin donatit skin cells. The newborn mice received several injections, ilka ane containin aboot 100,000 human brain cells, intae the space whaur their ain brain tissue was missin. In total, the rodents lackit aboot 14m mouse brain cells and endit up wi aboot 4m human anes – hauf the brain by volume.

Three months after surgery, the human tissue had hookit up tae the mouse’s bluid supply and amaist entirely fillit the cavity, takin up aboot hauf the size o the rodent’s brain. Some o the human neurons formed connections wi mouse brain cells and spinal cord.

The human neurons wur no structured or wired up in the same way as in folk, and the brain tissue was immature, equivalent tae that fund haufway through human pregnancy. Tests on the xenocortical mice shawed the animals wur no enhanced by the transplants, but their shaky gait and cognitive problems did improve a wee bittie.

Tae demonstrate hou the mice cud shed licht on human brain disorders, the researchers expost some o the animals tae five oors o law oxygen. This shawed hou vulnerable human nerve cells are tae oxygen deprivation, which in pregnancy and birth can cause cerebral palsy.

The researchers fund that human brain tissue in the mice containit rare cells kent as von Economo neurons, which hae only been seen in postmortem examinations. The cells are amang the first tae dee in frontotemporal dementia, a rare form o the disease, which Pașca nou howps tae study in xenocortical mice.

Prof Madeline Lancaster, group leader at the MRC Laboratory o Molecular Biology in Cambridge, said the approach was best suitit tae questions aboot disorders and treatments whaur a hale animal was needit. “It is less clear tae me hou this will inform our unnerstandin o human brain development since it is rather artificial, and no at a like hou the brain develops naturally,” she said.

Mony researchers workin on brain organoids are growin thaim in vitro, or in dishes. The howp is they help tae reduce the number o animals usit in research. “It is obviously ethically sensitive and there needs tae be a vera guid reason tae dae this type o animal experimentation, which maist scientific avenues dae no require,” Lancaster addit. “The field is still aimin for fully in vitro solutions, but this wark can also inform on what may be needit tae improve those in vitro models tae reach mair mature stages.”