Researchers have created mice with half-human brains in an effort to understand and develop new treatments for conditions such as schizophrenia, epilepsy, cerebral palsy, intellectual disability, and rare forms of dementia, according to The Guardian. The technique allows scientists to take cells from patients with brain disorders, turn them into brain tissue in a laboratory, and grow that tissue inside living animals.
Stanford Researchers Transplant Lab-Grown Human Brain Cells Into Mice
Writing in Nature, Stanford University neuroscientists described how they transplanted lab-grown human brain organoids into animals that were genetically engineered to be born without a cerebral cortex or hippocampus. In previous work, the Stanford team transplanted human neurons into rat brains, but found there was too little room for the human tissue to grow because human brain cells develop at least 20 times slower than mouse cells and were outcompeted. By breeding genetically engineered mice missing key brain regions — termed “apallial” mice — the researchers removed this biological competition.
Growth and Integration of Human Neurons in Xenocortical Mice
Newborn mice received several injections, each containing about 100,000 human brain cells derived from reprogrammed skin cells, into the vacant cranial space, as reported by The Guardian and yahoo.com. The resulting animals are referred to by researchers as “xenocortical” mice.
Three months after surgery, the human tissue hooked up to the mouse’s blood supply, expanded dramatically, and made up more than 90 percent of the cortical tissue by volume, according to yahoo.com. In total, the rodents lacked about 14 million mouse brain cells and gained about 4 million human ones, The Guardian notes. Some human neurons formed connections with mouse brain cells and the spinal cord, and researchers detected human-derived cells with the distinctive elongated morphology of von Economo neuron-like cells. However, the human brain tissue was immature and equivalent to that found halfway through human pregnancy.
Behavioral Adaptations and Disease Research Implications
Despite lacking a cerebral cortex, the apallial mice developed alternative strategies using remaining brain parts and displayed good locomotion, though they performed less well in memory tasks, according to NPR. Mice with human brain cells also showed differences compared to regular, unaltered mice, such as having trouble walking properly after their brains were deprived of oxygen — a condition regular mice are resilient to.
Paşca noted that it remains unclear what specific aspects of the mouse brain encourage the human tissue to develop in this manner, suggesting that access to distant targets in the nervous system or other in vivo factors provide signals missing in petri dish organoids.
Ethical Considerations and Oversight
The work has sparked ethical discussions regarding animal welfare and whether clumps of neural tissue could become conscious or feel pain, The Guardian reports. Paşca stated that the project received extensive ethical oversight from the start. Experts emphasized that monitoring must continue, with Emily Jackson, professor of law at the London School of Economics and chair of a recent report on neural organoids for the Nuffield Council on Bioethics, noting that animal welfare is a critical concern requiring close evaluation.
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