They may sound like something out of "Doctor Who," but organoids are far from science fiction. These 3D structures, or “organ buds,” are lab-grown bundles of cells that resemble an organ, and are used to study human development, test out drugs and understand disease. Using sophisticated tissue culture techniques, scientists have impressively managed to grow mini livers, hearts and parts of the intestine.
Now, researchers have grown miniaturized versions of the brain, and they even behave like the real thing, offering scientists the rare opportunity to study functional human brain tissue. Not only do these so-called “human cortical spheroids” display remarkable similarity to the structure and organization of the human cerebral cortex—the region responsible for higher-order functions like language, thinking, perceiving and information processing—but they also possess working neurons capable of transmitting signals to one another.
Scientists hope that these tiny free-floating “brains” will help further our knowledge of how the nervous system develops and allow researchers to pick apart the mechanisms contributing to certain neuropsychiatric diseases, such as autism and schizophrenia.
“One of the major problems in understanding mental disorders is that we can’t directly access the human brain,” lead researcher Sergiu Paşca said in a statement. “These spheroids closely resemble the three-dimensional architecture of the cortex and have gene-expression patterns that mimic those in a developing fetal brain.”
While useful, there’s a limited amount of information we can glean from brain scans and post-mortems, but scientists believe that organoids could hold the potential for more detailed analyses of how certain brain regions develop, function and go awry. Significant progress has been made in the field, but scientists have struggled to create 3D cultures of brain cells, and 2D models fail to recapitulate the architecture or complexity of neuronal circuits required to gain meaningful data.
With the goal of producing more structurally and functionally relevant brain organoids, researchers from Stanford University first took skin cells from five people and converted them into blank slate cells called induced pluripotent stem cells (iPSCs). These cells are useful because they possess the ability to turn into virtually any type of cell found in the body.
After giving the cells a chance to grow in monolayers, they were removed and added to a special type of dish that prevents them from easily sticking to surfaces and thus encourages growth in 3D. The cells soon began to aggregate and create small, spherical colonies, so the researchers added a cocktail of molecules to encourage them into becoming immature brain cells. Over time, these differentiated into both neurons and a type of star-shaped cell called an astrocyte. These cells wrap around the connections between neurons, or synapses, and play a variety of crucial roles such as providing cells with metabolic support and regulating signal transmission.
When the researchers sliced these balls of cells, they found a 3D arrangement similar to what would be found in the human cortex, the researchers report in Nature Methods. But most importantly, functional tests revealed that 80% of the neurons in the spheroids could fire signals when stimulated, and 86% participated in network activity and displayed spontaneous activity similar to what we observe in the brain.
This research is still in its infancy, and we’re still a long way off from replacing animals in the lab, but the possibility of growing these structures from individual patients’ cells opens up doors for personalized medicine, meaning that treatments are more likely to be effective. Furthermore, they may help us fill in the gaps about the biochemical and developmental changes that are thought to contribute to certain brain disorders, like epilepsy.