Stanford researchers grow human brain tissue in mice in xenocortication study

Human brain tissue grown from stem cells and transplanted into mice has offered a new way to study the developing human brain. A study published in September in Nature by Sergiu Pașca's group at Stanford University details an experiment where human brain tissue was placed into mice whose cerebral cortex was genetically prevented from forming.

The Experiment

The transplanted tissue grew into the vacant space, produced several types of human brain cells, became electrically active, and connected with the mouse nervous system. Because the mice lacked a functioning immune system and much of their own neocortex and hippocampus, the human grafts expanded substantially, making up about 92% of the animal's cortical tissue by three months. The grafts generated deep-layer neurons carrying the molecular signature of von Economo neurons, which are found in humans and large-brained mammals but are absent in rodents. The researchers call this approach xenocortication.

Limitations and Testing

The researchers emphasize that they have not created a human brain inside a mouse, as the tissue remained immature and lacked the ordered structure of a normal human cortex. When exposed to five hours of severe oxygen deprivation, a molecular marker of oxygen stress appeared only in the human tissue. While the study found measurable differences in behavior using a machine-learning system called Motion Sequencing, it does not prove that human neurons directly caused any particular behavior.

Context

Studying human brain development helps scientists understand both evolutionary biology and medical conditions like psychiatric disorders that begin early in life. Laboratory-grown organoids usually lack blood circulation and sensory inputs, leading researchers to explore living host environments. Ethical questions remain about how far such experiments should go as future models develop more integrated neural tissue.