Mental disorders like autism and schizophrenia are notoriously difficult to study at the molecular level. Understandably, people are reluctant to donate pieces of living brain for study, and postmortem tissue lets researchers see the structure, but not the function, of the cells.
Now researchers in the laboratories of psychiatrist Sergiu Pasca, MD, and neurobiologist Ben Barres, MD, PhD, have found a way to make balls of cells that mimic the activity of the human cortex. They use a person’s skin cells, so the resulting “human cortical spheroid” has the same genetic composition as the donor. The research was published in Nature Methods yesterday.
According to our release:
Previous attempts to create patient-specific neural tissue for study have either generated two-dimensional colonies of immature neurons that do not create functional synapses, or required an external matrix on which to grow the cells in a series of laborious and technically difficult steps.
In contrast, the researchers found they were able to easily make hundreds of what they’ve termed “human cortical spheroids” using a single human skin sample. These spheroids grow to be as large as 5 millimeters in diameter and can be maintained in the laboratory for nine months or more. They exhibit complex neural network activity and can be studied with techniques well-honed in animal models.
The researchers, which include neonatology fellow Anca Pasca, MD, and graduate student Steven Sloan, hope to use the technique to help understand how the human brain develops, and what sometimes goes wrong. As described by Barres:
The power and promise of this new method is extraordinary. For instance, for developmental brain disorders, one could take skin cells from any patient and literally replay the development of their brain in a culture dish to figure out exactly what step of development went awry — and how it might be corrected.
The research is starting to garner attention, including this nice article from Wired yesterday. Pasca’s eager to note, however, that he’s not working to create entire brains, which would be ethically and technically challenging, to say the least. But simply generating even a few of the cell types in the cortex will give researchers a much larger canvas with which to study some devastating conditions. As Pasca notes in our release:
I am a physician by training. We are often very limited in the therapeutic options we can offer patients with mental disorders. The ability to investigate in a dish neuronal and glial function, as well as network activity, starting from patient’s own cells, has the potential to bring novel insights into psychiatric disorders and their treatment.
Previously: More than just glue, glial cells challenge neuron’s top slot and Star-shaped cells nab new starring role in sculpting brain circuits
Photo of spheroid cross-section by Anca Pasca