Here’s how Stanford scientists got human brain tissue to thrive in mice to advance neuroscience research

Researchers at Stanford Medicine have achieved a groundbreaking feat by transplanting self-organizing human brain tissue, known as cortical organoids, into specially engineered mice with most of their cerebral cortex missing. The cerebral cortex, the outer layer of the brain, is responsible for higher-level functions such as awareness, reasoning, language, attention, and decision-making.

The missing cerebral cortex in the mice's brains proved to be an ideal environment for the human tissue. The scientists observed that the human tissue not only survived but also thrived, grew, and formed working connections with the mice's brain, even extending to the spinal cord. This development has provided neuroscientists with a unique opportunity to study disease-associated alterations in human brain circuitry within an intact nervous system.

One of the most surprising findings was the presence of an important nerve cell type in the mice that had not been observed in laboratory cultures before. This discovery opens up new avenues for research into the underlying biological causes of conditions such as schizophrenia, epilepsy, autism, and cerebral palsy. The researchers believe that their methodology will enable a deeper understanding of the causes and mechanisms of neurodevelopmental and pregnancy-incurred disorders, as well as the testing of potential interventions to correct or prevent these conditions.

Profound autism affects one in every 218 American children, causing significant challenges in daily life. The researchers, led by Sergiu Pasca and Alison Singer, developed "xenocortical" mice to study the vulnerability of human cortical nerve cells to oxygen deprivation, which can cause brain injury during pregnancy or around birth. While animal models have been helpful, the researchers acknowledge that some biological features are uniquely human.

The study's limitations include the inability to study complex human behavior in a dish. To address this, the researchers propose integrating human organoids into a living rodent's brain during an early stage of circuit formation. In 2022, the team successfully transplanted human cortical organoids into newborn mice's brains, with the organoids occupying one-third of the mouse brain hemisphere six months later.

The implanted neurons were larger, more electrically active, and displayed more sophisticated branching patterns compared to those grown in a dish.