Scientists Are Using Patients' Skin Cells to Create Mini Brains

by Monica Joshi

Remember all those horror movies with brains floating in vats? It was always a little mysterious where those brains came from. Science fiction seemed so cool and gross all at the same time. Researchers are now creating 3D structures, "organ buds", that are lab-grown bundles of cells that resemble an organ. They are being used to study human development, test out new drugs and understand disease in general. Researchers from Stanford University have already managed to grow mini livers, hearts and even parts of the intestine.

The new research, published in the journal Nature Methods , describes how the researchers have grown miniaturized versions of the brain. As the mini brains behave like the real thing, scientists have the rare opportunity to study and experiment on functional brain matter. The brains have quite a striking similarity to the functioning of the cerebral cortex, the region of the brain that is responsible for higher-order functions like language, thinking, perceiving and information processing. The mini brains also possess working neurons that are capable of transmitting signals to one another.

Stanford University’s School of Medicine doctor, Sergiu Paşca, his wife, doctor Anca Pasca, and graduate student Steven Sloan, are the lead authors of “Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture" in which they explain their method for creating these organoids.

The researchers first took skin cells from five people. They then converted them into blank slate cells or induced pluripotent stem cells (iPSCs). The iPSCs possess the ability to turn into virtually any type of cell in the body. Finally, after giving the cells time to grow in monolayers, they were removed and added to a special type of dish that encourages 3D growth. As the cells began to aggregate and create small, spherical colonies, the researchers added a mix of molecules to help them develop into mini brain cells. These cells differentiated into both neurons and astrocyte. The star-shaped astrocyte cells wrap around the connections between neurons and provide cells with metabolic support, as well as regulate signal transmission.

The true test was that when the researchers sliced these balls of cells, they found a 3D arrangement similar to what would be found in the human cortex. More significantly, the functional tests revealed that 80% of the neurons in the spheroids could fire signals when stimulated. Also, 86% participated in network activity and displayed spontaneous activity similar to what we observe in the human brain.

This research has two major implications for the traditional lab-like setting. The first is that it could help us further our knowledge about how the nervous system develops and allow for more understanding about the mechanisms contributing to certain psychiatric diseases.
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.

As lead researcher, Sergiu Paşca, said:

“One of the major problems in understanding mental disorders is that we can’t directly access the human brain. These spheroids closely resemble the three-dimensional architecture of the cortex and have gene-expression patterns that mimic those in a developing fetal brain.”

The second is that this new research could be a way to replace animals in the lab, since the possibility of growing these brains from individual patients' cells opens up doors for personalized medicine. The treatments are more likely to be effective, as the research on mini brains can fill in the gaps about the biochemical and developmental changes taking place in certain brain disorders such as autism, epilepsy and schizophrenia.