For the first time, miniature human brains grown from stem cells and transplanted into living mice have been shown to respond to what the mice see. Scientists were able to watch the reaction in real time thanks to special graphene electrodes.
In recent years, scientists have discovered a way to revert adult skin cells to an immature state, after which they can be induced to form almost any other type of cell in the body. Stem cells can be used to create small but functional versions of organs called organoids in the laboratory.
Organoids can be used to model development, disease, and drug response with greater accuracy than using flat plate cultures of cells in dishes, as organoids provide a more natural, three-dimensional representation of the real thing. Over the years, scientists have successfully grown mini versions of brains, hearts, lungs, livers, kidneys, stomachs, eyes, pancreases, and even blood vessels and hair follicles.
Last October, a team from Stanford University transplanted human brain organoids into rats for the first time and found that human cells form connections with rat neurons. In a new study, scientists at the University of California (UC) San Diego have expanded that work by showing that human brain organoids implanted in mice can respond to stimuli.
Previously, this was difficult to see because the associated brain activity lasted for milliseconds, and was difficult to capture with existing techniques. So a team at the University of California, San Diego, he combined two experimental techniques to image brain cells.
First, we placed an array of transparent graphene electrodes over the transplanted organoids. These devices allowed the team to record electrical neural activity taking place in both human brain cells and surrounding mouse brain tissue. They then used two-photon microscopy to image the brain and found that blood vessels in mice grew into organoids, supplying them with oxygen and nutrients.
David Baylot
Three weeks after implantation, the researchers conducted an experiment, flashing a white light in front of the mice and observing the reactions of various brain cells. And indeed, the graphene electrodes showed clear signs of electrical spikes propagating from the visual cortex. This indicates that the human organoids formed synaptic connections with the surrounding mouse brain tissue. In 11-week follow-up experiments, the team showed that the implants were increasingly functionally integrated into the host.
“No other study has been able to simultaneously record optically and electrically,” said Madison Wilson, the study’s lead author. “Our experiments revealed that visual stimuli elicited electrophysiological responses in organoids, consistent with responses from the surrounding cortex.”
In future studies, the team plans to use this technique to model the progression of neurological disorders, which could ultimately help uncover new potential treatments.
A study was published in a journal Nature Communications.
Source: University of California, San Diego
