Leap forward for brain research
Human tissue implanted in rats offers gold mine
Scientists have successfully implanted and integrated human brain cells into newborn rats, creating a new way to study complex psychiatric disorders such as schizophrenia and autism, and perhaps eventually test treatments.
Studying how these conditions develop is incredibly difficult: Animals do not experience them like people, and humans cannot simply be opened up for research.
Scientists can assemble small sections of human brain tissue made from stem cells in petri dishes, and have already done so with more than a dozen brain regions.
But in dishes, “neurons don’t grow to the size which a human neuron in an actual human brain would grow,” said Sergiu Pasca, the study’s lead author and professor of psychiatry and behavioral sciences at Stanford University.
And isolated from a body, they cannot tell us what symptoms a defect will cause.
To overcome those limitations, researchers implanted the groupings of human brain cells, called organoids, into the brains of young rats.
The rats’ age was important: Human neurons have been implanted into adult rats before, but an animal’s brain stops developing at a certain age, limiting how well implanted cells can integrate.
“By transplanting them at these early stages, we found that these organoids can grow relatively large, they become vascularized [receive nutrients] by the rat, and they can cover about a third of a rat’s [brain] hemisphere,” Pasca said.
To test how well the human neurons integrated with the rat brains and bodies, air was puffed across the animals’ whiskers, which prompted electrical activity in the human neurons.
That showed an input connection – external stimulation of the rat’s body was processed by the human tissue in the brain.
The scientists then tested the reverse: Could the human neurons send signals back to the rat’s body?
They implanted human brain cells altered to respond to blue light, and then trained the rats to expect a “reward” of water from a spout when blue light shone on the neurons via a cable in the animals’ skulls.
After two weeks, pulsing the blue light sent the rats scrambling to the spout, according to the research published on Wednesday in the journal Nature.
The team has now used the technique to show that organoids developed from patients with Timothy syndrome grow more slowly and display less electrical activity than those from healthy people.
Tara Spires-Jones, a professor at the University of Edinburgh’s UK Dementia Research Institute, said the work “has the potential to advance what we know about human brain development and neurodevelopmental disorders.”
