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(AP) - Scientists have transplanted human brain cells into the brains of baby rats, where the cells grew and formed connections.
It’s part of
an effort to better study human brain development and diseases affecting this
most complex of organs, which makes us who we are but has long been shrouded in
mystery.
“Many
disorders such as autism and schizophrenia are likely uniquely human” but “the
human brain certainly has not been very accessible,” said said Dr. Sergiu
Pasca, senior author of a study describing the work, published Wednesday in the
journal Nature.
Approaches
that don’t involve taking tissue out of the human brain are “promising avenues
in trying to tackle these conditions.”
The research
builds upon the team’s previous work creating brain “organoids,” tiny
structures resembling human organs that have also been made to represent others
such as livers, kidneys, prostates, or key parts of them.
To make the
brain organoids, Stanford University scientists transformed human skin cells
into stem cells and then coaxed them to become several types of brain cells.
Those cells then multiplied to form organoids resembling the cerebral cortex,
the human brain’s outermost layer, which plays a key role in things like
memory, thinking, learning, reasoning and emotions.
Scientists
transplanted those organoids into rat pups 2 to 3 days old, a stage when brain
connections are still forming. The organoids grew so that they eventually
occupied a third of the hemisphere of the rat’s brain where they were
implanted. Neurons from the organoids formed working connections with circuits
in the brain.
Human
neurons have been transplanted in rodents before, but generally in adult
animals, usually mice. Pasca, a psychiatry professor at the Stanford School of
Medicine, said this is the first time these organoids have been placed into
early rat brains, creating “the most advanced human brain circuitry ever built
from human skin cells and a demonstration that implanted human neurons can influence
an animal’s behavior.”
To examine a
practical use of this approach, scientists transplanted organoids into both
sides of a rat’s brain: one generated from a healthy person’s cells and another
from the cells of a person with Timothy syndrome, a rare genetic condition
associated with heart problems and autism spectrum disorder.
Five to six
months later, they saw effects of the disease related to the activity of the
neurons. There were differences in the two sides’ electrical activity, and the
neurons from the person with Timothy syndrome were much smaller and didn’t
sprout as many extensions that pick up input from nearby neurons.
Researchers,
whose study was funded partly by the National Institutes of Health, said they
could do the same sorts of experiments using organoids made from the cells of
people with disorders such as autism or schizophrenia — and potentially learn
new things about how these conditions affect the brain, too.
Dr. Flora
Vaccarino of Yale University – who previously grew lumps containing cerebral
cortex that were made with DNA from people with autism – said the study moves
the field forward.
“It’s
extremely impressive what they do here in terms of what these cells can
actually show us in terms of their advanced development … in the rat,” said
Vaccarino, who wasn’t involved with the study.
Such
experiments in animals raise ethical concerns. For example, Pasca said he and
his team are cognizant of the rats’ well-being and whether they still behave
normally with the organoids inside them, which he says they do. Still, Pasca
does not believe this should be tried in primates. Ethicists also wonder about
the possibility of brain organoids in the future attaining something like human
consciousness, which experts say is extremely unlikely now.
Some
scientists are studying human brain organoids outside of animals. For example,
researchers at ETH Zurich in Switzerland published a study in Nature earlier
this month describing how they are growing brain-like tissue from stem cells in
the lab and then mapping the cell types in various brain regions and genes
regulating their development. Some are using these structures to study autism.
Pasca said
brain organoids could also be used to test new treatments for neuropsychiatric
disorders, the largest cause of disability worldwide. Such research, he said,
should help scientists make strides that have been extremely difficult until
now because it’s so hard to get at the human brain – which is “the reason why
we’re so much more behind in psychiatry compared to any other branch of medicine
in terms of therapeutics.”
The
Associated Press Health and Science Department receives support from the Howard
Hughes Medical Institute’s Department of Science Education. The AP is solely
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