Lab-Grown Brain Clusters Could Shed Light on Disease

Stanford researchers are exploring a technique that allows them to culture and grow 3-D structures in a dish, enabling an increased understanding of mental disorders and illnesses.

It’s alive! It’s alive!

Those words from the 1931 film iteration of Frankenstein come to mind when hearing about the recent work of Stanford University researchers, who have developed living clusters of brain tissue on a Petri dish.

The new “disease-in-a-dish” technology that is currently underway at Stanford could shed light on the workings of the brain’s cortex and improve our molecular-level understanding of diseases like autism and schizophrenia.

The study, led by Stanford researcher Sergiu Pasca, MD, reveals details about what his team refers to as “human cortical spheroids.” Pasca’s team were able to perfect mini cultured 3-D structures that grow and function like the cortex of the human brain from which they were extracted from. Their research found that these “organoids” buzz with neuronal network activity, much like they do in our brains, allowing for a heightened modeling and understanding of brain circuitry, according to an NIH news release.

The NIH is promoting the Brain Research through its Advancing Innovative Neurotechnologies (BRAIN) initiative, a project aimed at revolutionizing our understanding of the human brain. The project has already seen endeavors such as therapeutic electric brain implantsreceive an increase in funding.

Thomas R. Insel, MD and director of NIH’s National Institute of Mental Health, spoke in the news release about the research and its implications for the future. “The cortex spheroids grow to a state in which they express functional connectivity, allowing for modeling and understanding of mental illnesses,” he said. “They do not even begin to approach the complexity of a whole human brain, but that is not exactly what we need to study disorders of brain circuitry. As we seek advances that promise enormous potential benefits to patients, we are ever mindful of the ethical issues they present.”

Before Pasca’s research, scientists had developed a similar technique to study neurons differentiated from stem cells that derived from patients’ skin cells, using a technology known as induced pluripotent stem cells (iPSCs). While this method did produce primitive organoids by coaxing neurons and support cells to organize themselves, they lacked the complex circuitry required to even begin to mimic the workings of the human brain.

Pasca’s team was able to use that technique as a jumping off point for their own research, before streamlining the method to produce cortex-like spheroids that could harbor healthier neurons that were supported by a more naturalistic network of supporting glial cells, which resulted in more functional neural connections and circuitry. The neurons began forming layers and talking with each other through neural networks, as the spheroids generated the same kinds of cortex-like structures in repeated experiments.

While the technology is still in its infancy, researchers believe there is significant potential for using these assays to develop and test the safety and effectiveness of new treatment options before they are used on patients with a mental illness. The group hopes to develop multiple neuron subtypes that normally populate the cortex, as well as long-distance connections between this cortex-like structure and other organoid structures. The research could not only pave the way toward an increased understanding of the brain, but also enhance the effectiveness of treatment options for patients who suffer from debilitating brain conditions and mental illnesses.