What Human Brain Tissue Transplanted Into Mice Showed Us, PgII

Key Highlights:

• A study published in Nature by neuroscientist Sergiu Pașca’s group at Stanford University successfully transplanted human brain tissue into genetically modified mice.
• The human tissue, grown from induced pluripotent stem cells, was placed into mice whose cerebral cortex and hippocampus were genetically prevented from forming.
• This novel approach, termed xenocortication, allowed the human grafts to expand significantly, comprising about 92% of the animal’s cortical tissue.
• The transplanted human brain cells became electrically active, formed connections with the mouse nervous system, and included specialized von Economo neurons.
• The experiment demonstrated measurable behavioral differences in the mice and offers a new platform for studying human brain development and neurological disorders.

Human Brain in Mice.jpg

Detailed Insights:

• The mice were specifically bred to lack a functioning immune system, preventing the rejection of the transplanted human tissue.
• The human grafts reached a stage of maturity roughly equivalent to the human cortex late in the second trimester of pregnancy.
• Functional integration was observed, with human nerve fibers extending as far as the cervical spinal cord, a significant finding.
• The platform enables researchers to introduce disease-related mutations, observe cellular changes, assess behavioral impacts, and test potential treatments.
• This model can aid in studying developmental brain disorders, oxygen deprivation injuries, human-specific neuronal diseases, and evolutionary differences in brains.
• Ethical considerations regarding potential alterations to animal cognition and perception were raised, necessitating careful scrutiny for future, more advanced experiments.

Scientific/Technical Concepts Involved:

• Induced pluripotent stem cells: Adult cells reprogrammed to an embryonic-like state, capable of differentiating into various cell types.
• Organoids: Miniaturized, simplified versions of organs produced in vitro from stem cells, mimicking some features of the real organ.
• Xenocortication: An experimental approach involving transplanting human cortical organoids into genetically modified host animals lacking their own cortex.
• Cerebral cortex: The outer layer of the cerebrum, playing a key role in memory, attention, perception, cognition, awareness, thought, language, and consciousness.
• Von Economo neurons: Large, spindle-shaped neurons found in specific regions of the brains of humans and some other large-brained mammals, associated with social cognition.