Stanford researchers grow human brain tissue in mice for disease modeling

Scientists at Stanford Medicine have successfully grown human brain tissue inside mice, with the transplanted cells making up to 50% of the brain by volume, according to a study published in Nature. The approach involves reprogramming skin cells from patients into neural cells, injecting them into newborn mice that lack a cerebral cortex and hippocampus, and allowing the human neurons to integrate with the animal’s circulatory system.

The engineered mice survive with other brain regions compensating for the missing structures, and the human cells develop into roughly four million neurons that form connections with mouse brain cells and the spinal cord. The tissue remains immature, comparable to a mid-gestation human fetal brain, and does not confer cognitive enhancement, although the animals exhibit modest improvements in gait and memory.

To demonstrate the model’s utility, researchers exposed some mice to low-oxygen conditions that mimic prenatal hypoxia associated with cerebral palsy. The human neurons showed heightened sensitivity to oxygen deprivation. The team also identified von Economo neurons in the grafts, a cell type previously observed only in post-mortem studies and linked to frontotemporal dementia, which the researchers intend to investigate further.

"These animal models offer a unique opportunity to study how disease-associated alterations in human brain circuitry manifest in an intact nervous system," said Sergiu Pașca, professor of psychiatry and behavioral sciences at Stanford Medicine.

The project has been conducted under ethical oversight, adhering to International Society for Stem Cell Research guidelines and using donor-consented cells. Bioethicists, including members of the UK’s Nuffield Council on Bioethics, stress the need for ongoing monitoring of animal welfare and the broader ethical implications of creating chimeric brains.

Critics argue that growing human tissue in a rodent cavity may not accurately reflect natural human brain development and suggest that laboratory-based organoid models could reduce reliance on animal experiments.