A US research team has shown that human brain tissue implanted in mice can be integrated into the host’s brain, promising to give scientists a whole new way to study brain diseases — but also raising ethical questions.
Professor Sergiu Pasca of Stanford University in California and colleagues grew sesame-sized clumps of human brain cells, called “organoids,” in test tubes and implanted them into the brains of young mice.
In the study, published in the journal Nature, they report that human brain tissue not only survives, but also integrates itself into the rat brain, establishing connections with rat brain cells and being supplied by the rat’s bloodstream Provide services.
Organoids also grew in rat brains, about the size of a pea.
Human nerve cells grew in rats about six times as much as in test tubes.
The team then conducted a series of experiments showing that human brain cells can receive sensory signals from the rat whiskers, but can also send instructions to other parts of the rat brain after being trained.
“They can receive sensory input, but they are also involved in some neural circuits in mice,” Professor Pascal said.
The research group’s goal is to develop “in vivo” models for studying the human brain and its diseases.
The complex cellular or chemical underpinnings of brain disorders such as autism and schizophrenia are difficult to study in human subjects. Mice and mice are poor substitutes for the human brain, and research using primates is ethically dubious.
While organoids in test tubes have shed new light on how nerves work at the cellular level, they have never grown as large or complex as healthy human brain tissue.
But researchers hope that growing human brain organoids in another species is closer to seeing the inside of a human brain. Especially when testing new drugs for brain diseases.
Professor Pascal said: “Imagine using this model, you can test drugs on human cells in a non-invasive way ‘in vivo’.
But implanting human brain cells into animals raises profound ethical questions if research goes beyond that. The team said they did not observe differences in behavior between the rats that received the human brain grafts and those that didn’t.
Given the limited lifespan of mice, human brain tissue, which takes years to mature, can only develop so much.
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Most experts seem to think that, given the small size of the rat brain and the smaller size of the transplanted human tissue, the rat won’t even become part human — and that the number of human brain circuits is too small to have a consciousness of its own.
But experts say scientists will need oversight as the field develops.
“Key questions revolve around whether organoids can have consciousness and moral standing,” human organoid researchers J Gray Camp and Barbara Treutline wrote in an article accompanying the publication.
“Positive discourse is needed,” they wrote, “to develop frameworks and boundaries for research using organoids to mimic human brain circuits.”
An obvious next step could be putting human brain organoids inside primates.
Their brains were large enough to hold more human brain tissue and lived longer than mice whose brain cells had matured.
But, according to Prof Pascal, this is currently a red line: “Transplanting into primates is not something we would like to do, nor something we are encouraged to do.”