Imagine if scientists could manufacture a miniature human brain, allowing them to study the organ’s inner workings without the ethical or practical dilemmas associated with a live organ. This is the promise of organoids — small, three-dimensional tissue cultures derived from stem cells. Organoids allow researchers to essentially grow human tissue from scratch, evaluating it in a lab setting. Organoids aren’t limited to organs like brains or lungs, either; stem cells can replicate entire systems. Stanford Medicine investigators recently used organoid principles to replicate a prominent neural pathway that allows humans to sense pain. Read on to learn more about the study, which was published April 9 in Nature and could provide stunning new insights into human pain systems.
Evaluating the Neural Pathway Responsible for Pain
The Stanford study was led by Sergiu Pasca, MD, the Kenneth T. Norris, Jr., Professor II of Psychiatry and Behavioral Sciences. In a press release provided by Stanford Medicine, Pasca explained the need for pain-related organoids, noting that human pain is difficult to study in laboratory animals. “Their pain pathways are in some respects different from ours,” wrote Pasca. “Yet these animals experience pain. Our dish-based construct doesn’t.” In other words, lab-grown organoids offer a humane alternative to animal subjects.
In the study published in Nature, the authors describe their successful assembly of four organoids: miniaturized parts of the human nervous system meant to reconstitute the ascending sensory pathway, which transmits painful sensations from the skin to the brain.
Stanford Team Recreates Ascending Sensory Pathway via Organoids
To create effective sensory organoids, Pasca’s team had to replicate the distinct brain regions composing the ascending sensory pathway. To do so, the researchers leaned on Pasca’s previous research: specifically, the creation of what Pasca calls “regionalized neural organoids” to represent distinct brain regions. To connect these regions and mimic an entire system, Pasca worked to fuse different organoid types together in a dish, forming what Pasca calls “assembloids.” To form an assembloid mimicking the ascending sensory pathway, Pasca’s team took skin cell samples from volunteers, transforming them into pluripotent stem cells, which can be guided to become many different cell types. They then employed chemical signals to coax these cells into aggregating into small balls — neural organoids, representing each of the four regions of the pathway. They lined these organoids up side by side, allowing them to fuse into assembloids that, according to Pasca, looked like “tiny sausage links.”
Along the way, Pasca and his colleagues became the first researchers ever to watch information being transmitted through the entire sensory pathway. “You’d never have been able to see this wavelike synchrony if you couldn’t watch all four organoids, connected, simultaneously,” Pasca said. “The brain is more than the sum of its parts.”
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The Stanford study could transform how the medical community thinks about pain signals, particularly those involved in chronic pain — pain that persists when observable damage is no longer evident on the surface. Could chronic pain be related to changes in the ascending sensory pathway? This team now has the tools to find out. “We can now model this pathway non-invasively,” said Pasca. “That will, we hope, help us learn how to better treat pain disorders.”
To learn more about organoids and how they could revolutionize CNS drug discovery, sign up for our upcoming webinar “How 3D Organoids are Shaping the Future of Neuro Drug Discovery” or check out our recently established organoid platforms, which can already be used for in vitro research services.
The nitroglycerin-induced migraine model is readily available at Scantox Neuro for your pain research. Further in vitro pain models based on sensory neurons are currently under development.
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