Researchers at Stanford University have created genetically modified mice whose cortical tissue is more than 90 percent human in volume, in an experiment led by the Romanian-born neurologist Sergiu Pașca. The results were published in the journal Nature.
The team first engineered mice to lack most of their cerebral cortex and hippocampus, regions central to functions such as memory. Into that space, the scientists transplanted human cortical organoids — small structures of nervous tissue grown in the laboratory from stem cells. The human tissue not only survived but grew and connected with the animals' nervous systems. Roughly three months after transplantation, more than 90 percent of the cortical tissue volume in these animals was of human origin. Pașca and his team call them «xenocortical mice».
The experiment marks a step beyond the laboratory's earlier work. In 2022, Pașca's group showed that human brain organoids transplanted into the brains of newborn rats could survive and integrate into the animals' nervous systems. The new method seeks to overcome the main limitation of those experiments: the limited space available and the competition between human tissue and the host animal's own brain.
The modified mice appear relatively normal at first glance. Researchers did, however, observe certain problems with coordination and memory. After the human tissue was introduced, the animals showed different behavioral performances, which allows scientists to study more directly how human cells function inside a living nervous system.
The stakes are medical. The model could be used to study neurological and neuropsychiatric diseases and to test treatments. In a demonstration experiment, the researchers exposed the xenocortical mice to very low oxygen levels. The human brain tissue showed damage, and the animals developed problems with walking and balance, offering a possible model for studying brain injury caused by oxygen deprivation.
The team also made a rare finding: within the transplanted human tissue they identified von Economo neurons, extremely rare nerve cells associated with particular regions of the human brain and implicated in complex functions.
The experiment also raises ethical questions. Pașca cautioned that such research should not be extended, in its current form, to primates. The closer an animal is to humans in evolutionary terms, the more pressing the question of whether a large volume of functional human brain tissue could significantly alter the animal's cognitive abilities. For now, the researchers say the xenocortical mice show no evidence of human cognitive capacities.
The aim of the experiment is different: to create a model in which scientists can observe, in a living organism, how human brain tissue develops and functions and how it responds to disease or injury. Pașca, who was born in Romania and works at Stanford, stands at the center of research that seeks to bring the laboratory closer than ever to the mysteries of the human brain.