Healthcare (Commonwealth Union) – Scientists from the Northwestern University have created what they describe as the most sophisticated organoid model yet for studying human spinal cord injury.
In the new research, the team worked with laboratory-grown human spinal cord organoids — tiny, stem cell–derived structures that replicate key features of real organs — to simulate various forms of spinal cord damage and evaluate a promising regenerative treatment.
For the first time, the scientists showed that these human spinal cord organoids can closely reproduce the main biological consequences of spinal cord injury, including cell loss, inflammation, and the formation of glial scars — thick scar tissue that acts as both a physical and chemical barrier to nerve regrowth.
When the damaged organoids were treated with so-called “dancing molecules” — an experimental therapy that previously restored movement and repaired tissue in animal studies — researchers observed substantial neurite growth, the long neuronal projections that allow nerve cells to communicate. In addition, the scar-like tissue within the treated organoids was significantly reduced. The findings strengthen optimism that the therapy, which recently received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA), could lead to better recovery prospects for people with spinal cord injuries.
The findings were published on 11 February in the journal Nature Biomedical Engineering.
“One of the most exciting aspects of organoids is that we can use them to test new therapies in human tissue,” explained Samuel I. Stupp, the study’s senior author and inventor of dancing molecules of the Northwestern University. “Short of a clinical trial, it’s the only way you can achieve this objective. We decided to develop two different injury models in a human spinal cord organoid and test our therapy to see if the results resembled what we previously saw in the animal model. After applying our therapy, the glial scar faded significantly to become barely detectable, and we saw neurites growing, resembling the axon regeneration we saw in animals. This is validation that our therapy has a good chance of working in humans.”
A trailblazer in self-assembling materials and regenerative medicine, Stupp serves as Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine, and Biomedical Engineering at Northwestern University. He holds appointments at the McCormick School of Engineering, the Weinberg College of Arts and Sciences, and the Feinberg School of Medicine, and leads the Center for Regenerative Nanomedicine (CRN). The study’s first author is Nozomu Takata, a research assistant professor of medicine at Feinberg and a CRN member.
As the tiny organoid has provided a major breakthrough researchers can hold great hope towards future uses. Organoids are lab-grown, miniature versions of human organs created from induced pluripotent stem cells. Though not complete organs, they closely replicate the structure, cell diversity, and functions of real human tissues. Because of this high level of similarity, organoids are powerful tools for studying diseases, evaluating new treatments, and exploring how organs develop. Compared with animal or human testing, research using organoids is quicker and significantly more cost-effective.
While other scientists have produced human organoids to study spinal cord physiology, Stupp’s model marks a significant advance toward developing therapies for severe, paralysis-causing injuries. Measuring several millimeters across, the organoids were sufficiently large and developed to support an injury model.
Over several months, Stupp’s team cultivated spinal cord organoids from stem cells, enabling them to form complex structures such as neurons and astrocytes. They were also the first to incorporate microglia — immune cells of the central nervous system — to better replicate the inflammatory response associated with traumatic spinal cord injuries.
Moving forward the researchers hope to form much more advanced organoids to take further their model.
