Hi, how are you? Are you sitting down? Because boy, do I have news for you: Mice with human brains are now a thing. OK, it's not quite that — scientists implanted miniature human brain cells into mice brains and discovered that the two brains lived in harmony. This holds huge promise for understanding how we study the human brain going forward.
A new report published in Nature Biotechnology by scientists at the Salk Institute states that “Differentiation of human [...] stem cells to small brain-like structures known as brain organoids offers an unprecedented opportunity to model human brain development and disease [...] we established a method for transplanting human brain organoids into the adult mouse brain.” STAT reports that this is the first “successful implant of human cerebral organoids into the brains of another species, with the host brain supplying the lentil-sized mini cerebrums with enough blood and nutrients to keep them alive for months.”
As unsettling as the term “host brain” might be, scientists will likely further use this approach to study human brain development. Researchers hope to test whether or not the rodents will one day can serve as “cortical repair kits, replacing regions of the brain that have been injured or failed to develop normally,” STAT further reports.
The Scientist states that brain organoids, or mini brains, are small clusters of stem cells used in research to better understand and investigate the neural basis for neurological disorders and autism. When organoids are grown in a culture, they typically only survive for a few months, so their usefulness as models for real brains is limited. By transplanting the human organoids into the brains of mice, they continue to develop by “Sprouting life-sustaining blood vessels as well as new neuronal connections,” the study further states.
Lead study coauthor Fred Gage, a neuroscientist at the Salk Institute for Biological Studies in La Jolla, California, told The Scientist that he and his colleagues were pondering a solution for the brief shelf life of the experimental human brain tissue over the course of a few years. The potential for research was capped. “Those cells weren’t getting the blood and nutrients they needed to survive.” Gage had previously done research in Sweden in which he and a small team of researchers transplanted neuronal tissue into cavities made in rats’ brains to see if the tissue would grow — and it did. Building on his previous research, Gage had the idea to transplant the human organoid tissue into mouse brains, and it worked. According to Scientific American, about 80 percent of the implants survived, and were sprouting additional cell neurons within twelve weeks. By 14 days, most of the organoids had enough developed blood vessels — delivering oxygen and nutrients — to survive up to 233 days.
Michal Stachowiak of the State University of New York at Buffalo (SUNY), who previously created human cerebral organoids to study schizophrenia, calls this “an important initial step toward using organoids in regenerative medicine,” according to STAT. But bioethicists have questioned how the implants impact the intelligence and consciousness of the mice involved. According to tests run by the study’s researchers, however, the mice with human brain organoids implanted didn’t seem altered much by the implants — their intelligence and behavior continued on as distinctly mouse-like, STAT reports.
That said, a human brain organoid transplanted into a mouse’s brain cavity, can’t reach the size required to develop much complexity, according to STAT, and ethical questions remain as to how such research impacts its animal subjects. “The little suckers are not going to say ‘Hi’, says bioethicist Hank Greely of Stanford University, but such research begs the question “Of whether you are creating something human-ish that you have to take seriously in terms of according it dignity and respect — and figuring out what that even means,” Greely told STAT.
While ethical questions continue to arise alongside the advances being made in human brain-to-mouse research, scientists hope that the organoids will expand their understanding of how to repair myriad neurological conditions, including brain injuries, dementia, and strokes. Given how new this research is, though — there is a lot left to discover in terms of how the organoid transplants will affect medical studies moving forward, and also the mice serving as tiny vehicles of such discovery.