Sergiu Pašca and his team at Stanford University created mice with half-human brain tissue by transplanting lab-grown human brain cells into animals engineered to lack a cortex and hippocampus. The mouse brain cavities were designed to give the human tissue room to grow, and the result may help scientists study disorders with few treatments.
Pašca said the aim was to make human brain development and function accessible for investigation. He added: "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".
Stanford University study
The researchers first reprogrammed donated skin cells into human brain organoids, then placed them into newborn mice with several injections of about 100,000 human brain cells each. The injections went into the space left where the mice’s own brain tissue was missing. The rodents lacked about 14 million mouse brain cells and ended up with about 4 million human ones.
Three months after surgery, the human tissue had hooked up to the mouse’s blood supply and almost completely filled the cavity. It took up about half the size of the rodent’s brain. The mice survived because the remaining parts of the brain took on new roles, and the animals looked normal but were cautious on their feet and more forgetful.
Neural organoids ethics
The work builds on earlier Stanford University research that transplanted human neurons into rat brains, where the tissue took root and wired into brain circuits but had too little room to grow very much. This newer approach is tied to disorders such as schizophrenia, epilepsy, cerebral palsy, intellectual disability and rare forms of dementia, giving scientists living tissue to test how those conditions develop and how drugs might act on them.
Emily Jackson, a professor of law at the London School of Economics and chair of a recent report on neural organoids for the Nuffield Council on Bioethics, said: "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." The organoid field has also raised questions about consciousness and pain, so the experimental gain comes with limits that researchers will need to watch closely.
Pašca’s next questions
Pašca said the research had received extensive ethical oversight from the start. The open question is not whether human tissue can survive in a mouse brain; it already did. It is how far that tissue can reveal the biology of disease, and whether the changes seen so far can be turned into better tests for brain disorders that still lack enough treatments.
