The brain is an exceptionally complex organ. It forms and trims neural connections in ways that are mysterious yet unquestionably shape development, memory, and processing. It’s also highly resilient—people born without large chunks of their brains can turn out just fine, possibly due to the organ’s ability to reroute neural connections early in life.
But when the brain is injured and its resiliency pushed to a limit, there is only so much modern medicine can do. When blood flow to the brain is blocked like in the case of a stroke, brain tissue can die, leaving a husk of what was once there that is difficult to rewire.
Isaac Chen, a neurosurgery researcher and clinician at the University of Pennsylvania, has been interested in fixing injured brains since his medical school days. To him, it seems like the key to unlocking how to heal the brain lies in the organ’s structure.
“I don’t think that throwing in cells that lack any structure will ultimately be able to restore function optimally,” Chen told The Daily Beast. “And so that’s why we looked at organoids: More than anything else that I know of right now other than the brain itself, organoids have that structure of the brain.”
Organoids are three-dimensional structures grown in the lab that are made out of human skin and blood cells. These human cells have been reprogrammed to a stem-cell state where they are able to 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 came to the aid of the existing tissue. Their results were published on Feb. 2 in the journal Cell Stem Cell.
Most studies that probe the effects of organoid transplantation on 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 the brain tissue that previously existed in the region. They did this to test the organoid’s ability to both integrate with the rest of the rat’s brain and compensate for the injury it had sustained.
To verify that structure played an important role in these grafts, the researchers transplanted full, complete organoids and ones broken apart into individual cells; they found that the survival of the cells was much higher when the structure of the organoid was maintained.
One month after the transplant, the researchers noted that the grafted area looked similar to the surrounding brain, and blood vessels had grown into the organoid to supply it with oxygen. When Chen and his team attached electrodes to the rats to measure their brain activity, all 10 grafts showed neural activity with similar characteristics as those from two normal rats.
But the real test came when Chen and his team showed eight of the 10 transplanted rats a screen displaying a flashing light. Six of them displayed neural activity tied to the visuals, and a subset of these responded to even more subtle visual stimuli.
According to Chen, this shows “that the neurons are adopting sophisticated properties of the visual cortex—and that’s something that has not been shown with organoids.”
Already, Chen and his team are working on transplanting organoids with improved structures that take them one step closer to mimicking organisms’ brains. They are testing out different regions of the brain for these transplants and studying the factors that influence graft integration.
We’re years away from using organoids to treat humans, but one can imagine a future where surgeons have the option of healing patients’ injured brains with new neural tissue. Strokes, traumatic brain injuries, cancer, and other severe diseases will no longer be thought of as events that permanently alter one’s ability to think and process information.
“Ultimately, our goal is to be able to transplant something and it’d be very hard to tell that there was any difference between the organoid and the brain itself,” Chen said. “Right now, we can tell there’s a difference, but these are still the early days of organoid transplantation.”