Stanford University researchers have successfully transplanted lab-grown human brain organoids into mice genetically engineered without a cerebral cortex or hippocampus, creating rodents where human tissue comprises roughly half the brain by volume to advance research into psychiatric and neurological disorders.
Scientists have pushed the boundaries of neuroscience by growing human brain tissue inside living rodents (The Guardian). The approach aims to tackle conditions that have long lagged behind other medical fields in therapeutic development (The Guardian).
Overcoming Spatial Limits Through Genetic Engineering
Previous attempts to implant human neurons into rodent brains ran into a severe spatial roadblock. Because mouse brains mature at a much faster rate, the host tissue routinely crowds out the human graft, limiting both its size and eventual functionality (Gizmodo).
To solve this structural limitation, the Stanford team (Nature) used a breeding strategy (Nature) to engineer mice born without a cerebral cortex and hippocampus (Gizmodo). The rodents lacked a large number of mouse brain cells (The Guardian), leaving a natural cavity inside the skull (The Guardian). Although missing these key brain regions, the mammals survived because the remaining parts of the brain adapted and took on new roles (The Guardian).
Researchers then reprogrammed donated human skin cells into stem cells (The Guardian), which were cultured into three-dimensional brain organoids (Gizmodo). Newborn pups received several injections containing about 100,000 human brain cells each (The Guardian). Three months post-surgery, the human tissue hooked up to the host’s blood supply, expanded to fill the cavity, and ended up with about four million human cells—accounting for roughly half the brain by volume (The Guardian).
Investigating Complex Neurological Disorders
The overarching goal of the technique—dubbed xenocortication (Gizmodo)—is to create accessible living models for conditions such as schizophrenia, epilepsy, cerebral palsy, intellectual disability, and rare forms of dementia (The Guardian).
We’ve been trying really hard as a community to find therapeutic solutions for these conditions, but the reality is that in psychiatry and neurology we’ve been left behind [by] every single branch of medicine and we have fewer therapeutics than, again, every single branch of medicine.
Sergiu Pașca, professor of psychiatry at Stanford University
Pașca added that the human brain’s complexity and inaccessibility have historically hindered drug discovery (The Guardian). By growing patient-derived cells inside living hosts, researchers can study how disorders take hold in human tissue (The Guardian).
Behavioral Observations and Ethical Oversight
Following six months of development, scientists subjected the animals to basic behavioral tests in a small tabletop arena (BBC). The animals performed largely like normal mice (BBC), though observers noted they remained cautious on their feet and somewhat more forgetful (The Guardian). The human neurons were immature, matching the developmental stage of a human halfway through pregnancy (The Guardian).
They don’t have any enhancement.
Sergiu Pașca, director of the Stanford Brain Organogenesis Program
External bioethicists confirmed that the current iteration of the research shows no indication that what’s being created here are mice that can think like humans, or a human brain in a mouse body
(BBC). However, experts emphasize that the work raises important questions (BBC).
Animal welfare is a really important concern, and it will be necessary to closely monitor these animals in order to evaluate the impact on them.
Emily Jackson, professor of law at London School of Economics
Stanford project leads noted that the initiative has involved extensive institutional oversight from the outset (Gizmodo).