The brain is an exceptionally complex organ. It shapes and cuts neural connections in ways that are mysterious but undoubtedly shape development, memory, and processing. It’s also very resilient: People born without large portions of their brains can do just fine, possibly due to the organ’s ability to reroute neural connections early in life.
But when the brain is injured and its ability to recover is pushed to the limit, modern medicine can’t do much. When blood flow to the brain is blocked as in the case of a stroke, brain tissue can die, leaving a shell of what was once there that is difficult to rewire.
Isaac Chen, a neurosurgery researcher and physician at the University of Pennsylvania, has been interested in repairing injured brains since his days in medical school. It seems to him that the key to discovering how to heal the brain lies in the structure of the organ.
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“I don’t think adding cells that lack structure can ultimately restore function optimally,” Chen told The Daily Beast. “And that’s why we looked at organoids: more than anything else that I know of right now besides the brain itself, organoids have that structure of the brain.”
Organoids are three-dimensional structures grown in the laboratory that are made of human skin and blood cells. These human cells have been reprogrammed to a stem cell state where they can develop into multiple cell types. In a new study, Chen and a team of researchers transplanted brain organoids into the injured brains of rats and tested whether the new brain cells helped existing tissue. Their results were published on February 2 in the journal Cell Stem Cell.
Most studies investigating the effects of organoid transplantation in rodents have used very young mice and rats. In contrast, Chen and his colleagues transplanted organoids into the visual cortices, the parts of their brains responsible for vision, of 10 adult rats after sucking out previously existing brain tissue from the region. They did this to test the organoid’s ability to integrate with the rest of the rat’s brain and compensate for the injury it had sustained.
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To verify that structure played an important role in these grafts, the researchers transplanted whole and separate organoids into single cells; found that cell survival was much higher when the organoid structure was maintained.
One month after the transplant, the researchers noted that the grafted area resembled the surrounding brain, and that blood vessels had grown into the organoid to supply it with oxygen. When Chen and her team attached electrodes to the rats to measure their brain activity, all 10 grafts showed neural activity with characteristics similar to that of two normal rats.
But the real test came when Chen and his team showed eight of the 10 transplanted rats a screen that displayed a flashing light. Six of them showed image-linked neural activity, and a subset of them responded to even more subtle visual stimuli.
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According to Chen, this shows “that neurons are adopting sophisticated properties of the visual cortex, and that’s something that hasn’t been shown with organoids.”
Chen and his team are already working on transplanting organoids with improved structures that bring them one step closer to mimicking the brains of organisms. They are testing different brain regions for these transplants and studying factors that influence graft integration.
We are years away from using organoids to treat humans, but one can imagine a future in which surgeons have the option of healing patients’ injured brains with new neural tissue. Strokes, traumatic brain injuries, cancer, and other serious illnesses will no longer be considered events that permanently alter the ability to think and process information.
“Ultimately, our goal is to be able to transplant something, and it would be very difficult to know if there was any difference between the organoid and the brain itself,” Chen said. “Right now, we can say there is a difference, but these are still the early days of organoid transplantation.”
Read more at The Daily Beast.
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