Imagine holding the secrets of the human brain in the palm of your hand. Organoids — three-dimensional cell cultures that mimic the structure and function of human organs — accomplish just that. For nearly a decade, the Stanford Brain Organogenesis Program has pioneered this approach to studying the brain, specializing in neural organoids. The program has made significant strides in neurological research, unlocking the mysteries of pain responses, neurodevelopmental disorders, neural circuits, and more. The progress has, however, been somewhat limited by scale, due in part to neural organoids’ tendency to fuse together during the initial growth phase. A study published June 27 in Nature Biomedical Engineering found the answer to this sticky situation: xanthan gum, a common food additive.
Separating Sticky Organoids in Lab Settings
For large-scale data sets, scientists need large batches of neural organoids that are consistent in shape and size. Unfortunately, as mentioned above, organoids can get a bit sticky. Neural organoids have a habit of fusing together during the growth process, creating irregular clusters of varying shapes, sizes, and functions. This makes those large-scale data sets all but impossible.
Rather than grow each organoid in a separate dish — an inefficient process, especially for large data sets — the team behind the June 27 study needed to find a scalable way to avoid “undesired organoid fusion” while growing them in batches. To do this, they had to sort through dozens of substances that could be placed directly within the lab culture.
Household Baking Ingredient Topples the Competition
The team explored 23 different materials that would be biocompatible with neural organoids, as well as “relatively economical and simple to use,” allowing the method to be adopted easily by other scientists. They tested the substances one by one, growing organoids in a nutrient-rich liquid for six days before adding a substance. The researchers then waited 25 days and concluded each test by counting how many organoids remained — in other words, looking for undesired fusion.
In the end, the most effective substance was an astoundingly simple one: xanthan gum, which the team called a “cost-effective polysaccharide.” Xanthan gum is cheap and ubiquitous, widely used in baking as a thickening agent and stabilizer. And it worked beautifully, preventing organoids from fusing together without any negative impact on organoid development.
Real-Life Impact of Organoid Scaling
Once xanthan gum was identified as a viable substance to prevent organoid fusion, the researchers worked to demonstrate the find’s far-reaching impact. The best way to achieve this? Running a large-scale organoid study to test the effects of previously approved drugs on infant brain development. Co-lead author Genta Narazaki grew a massive set of 2,400 organoids in batches, then used the successful large-scale operation as an excuse to test 298 approved drugs to see if any of them might cause growth defects. In fact, several drugs did stunt the growth of the organoids, which could be valuable information for doctors working with pregnant patients — information that never would have been discovered without efficient scaling of neural organoid development.
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Moving forward, the Stanford Brain Organogenesis Program researchers hope to use organoids to explore a number of neuropsychiatric disorders, including epilepsy and schizophrenia. “Addressing those diseases is really important, but unless you scale up, there’s no way to make a dent,” said study lead Sergiu Pasca, the Kenneth T. Norris, Jr. Professor of Psychiatry and Behavioral Sciences in the Stanford School of Medicine. “That’s the goal right now.”
To perform organoid research, Scantox Neuro offers research with cerebral organoids to model accelerated aging and senescence and related analysis methods.
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