Artificially grown organoids are becoming more and more important in scientific and medical research. Now, scientists have measured activity similar to actual brain waves in lab-grown brain organoids while researching a genetic condition that causes seizures.
Such organoids can be useful for researching brain development, diseases, and potential therapies, because they can be involved in experiments that just wouldn't be possible with a living human brain.
In the new study, researchers reported patterns of electrical activity closely matching a seizure in brain organoids developed from the stem cells of patients with Rett syndrome – a genetic condition that can result in seizures in some cases.
"This work demonstrates that we can make organoids that resemble real human brain tissue and can be used to accurately replicate certain features of human brain function and disease," says neuroscientist Bennett Novitch, from the University of California, Los Angeles (UCLA).
To create organoids, scientists induce cells taken from humans to turn into pluripotent stem cells, a type of cell than grow into a wide variety of tissues and organs.
The process is particularly difficult in the brain, because there's so much going on. To be helpful for more types of research, besides getting all those neurons organized, these 'mini brain' organoids must also develop the same neural oscillations that occur in the human brain – waves similar to those associated with learning, sleep, and so on.
Now those waves have been spotted, increasing the likelihood that organoids can stand in for real brains in experimental research. In many neural diseases, the actual brain cells themselves look fine – it's the oscillations that indicate that something is wrong.
Using electrical probes and microscope readings, the researchers gave their newly created organoids something similar to an electroencephalogram (EEG) scan, revealing multiple kinds of neural oscillations.
"I hadn't anticipated the range of oscillation patterns we would see," says Novitch. "By learning how to control which oscillation patterns an organoid exhibits, we may be able to eventually model different brain states."
In the case of the abnormal oscillations seen in the organoids developed from people with Rett syndrome, adding the experimental drug Pifithrin-alpha removed the signs of seizures – so these organoids are able to 'respond' to treatment too. Throughout, the brain cells themselves looked normal, which is also the case with Rett syndrome.
It's another step forward for brain organoid technology and science, which continues to progress at a rapid pace. Only last week we saw a study outlining how eye structures had evolved in a mini brain grown in the lab, for example.
While brain organoids will never match the complexity or detail of actual brains, they could eventually replace animals in future studies, as long as we're sure these clumps of specially developed cells are close enough to what really happens in the brain.
"This is one of the first tangible examples of drug testing in action in a brain organoid," says neurologist Ranmal Samarasinghe, from UCLA.
"We hope it serves as a stepping stone toward a better understanding of human brain biology and brain disease."
The research has been published in Nature Neuroscience.