Human Brain Tissue Successfully Transplanted Into Mice, Offering a New Model for Neurological Disease Research

U.S. researchers have successfully transplanted human brain tissue into mice with almost no cerebral cortex, where it survived and grew. The model is drawing attention as a way to accelerate research into the causes of mental illness and neurodevelopmental disorders and the development of treatments.

According to Stanford Medicine on the 16th local time, a research team led by Professor Sergiu Pasca transplanted human brain organoids grown in the laboratory into the brains of mice genetically engineered to lack a cerebral cortex. The findings were published in the international journal Nature.

The team transplanted self-organizing human brain tissue, called “cortical organoids,” into mice bioengineered and bred to have almost no cerebral cortex. The cerebral cortex is the brain’s outermost layer and is responsible for higher functions such as cognition, language, attention and decision-making.

The transplanted human tissue survived and grew in the mouse brain, forming functional circuits that extended beyond the brain and into the spinal cord. Three months after transplantation, more than 90% of the cortical tissue in the mouse brain was made up of human cells.

“This animal model provides a unique opportunity to study how changes in disease-related human brain circuits manifest in an intact nervous system,” Pasca said.

The team hopes the methodology will advance research into the underlying biological causes of schizophrenia, epilepsy, severe autism and cerebral palsy. One in 20 U.S. adults has a serious mental illness, and more than 1 in 100 adults has schizophrenia.

In a proof-of-concept experiment, the team exposed mice with transplants to low-oxygen conditions for 5 hours. The human-derived cortical tissue sustained substantial damage, and the mice had difficulty walking and maintaining their balance. This resembles patterns observed in children with cerebral palsy.

“Identifying the cause of this difference could provide clues about the vulnerability of human neurons to oxygen deprivation and offer a platform for determining the mechanisms of cerebral palsy,” Pasca explained.

Von Economo neurons (VENs) were also found in the transplanted human tissue. These rare cells have so far been observed only in postmortem brain tissue and have never been generated through laboratory culture. They occur at a rate of about 1 per 90,000 cortical neurons.

“These cells appear to be particularly vulnerable in frontotemporal dementia, a neurodegenerative disease that can begin in middle age,” Pasca said. “We can now induce these rare cells from healthy people or patients and study them in living animals.”

The team said it consulted ethicists, neurobiologists, patient advocacy groups, philosophers and legal scholars to ensure that ethical boundaries were respected. Stanford University’s Office of Technology Licensing holds patents related to the generation of cortical organoids, and Pasca is listed as an inventor.