In a major advance for regenerative medicine, researchers at Northwestern University have developed the most advanced lab-grown human spinal cord that can mimic traumatic injury and respond to a promising new therapy.
The study, published February 11 in Nature Biomedical Engineering, demonstrates for the first time that human spinal cord organoids can replicate the complex biological damage seen in real spinal cord injuries.
The miniature tissue models responded positively to an experimental treatment known as dancing molecules, showing signs of nerve regeneration and reduced scar formation.
Organoids are miniature. These are the simplified versions of organs grown in the lab from induced pluripotent stem cells. While they are not full organs, they closely mimic the structure and cellular behavior of real human tissue.
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Scientists use them to model diseases, test therapies and explore organ development in ways that are faster and more cost-effective than animal or human trials.
The Northwestern team spent months cultivating spinal cord organoids large enough to simulate traumatic injury. These organoids developed complex networks of neurons and astrocytes, two key cell types in the central nervous system.
In a first for spinal cord models, the team also introduced microglia, immune cells that trigger inflammation after injury. It allowed the organoids to produce the same inflammatory chemicals found in real spinal trauma.
“It’s kind of a pseudo-organ,” said senior author Samuel I. Stupp, a pioneer in regenerative nanomedicine. “We were the first to introduce microglia into a human spinal cord organoid, so that was a huge accomplishment. It means our organoid has all the chemicals that the resident immune system produces in response to an injury.”
For the test, researchers simulated two common types of spinal cord trauma. In one method, they used a scalpel to create a laceration similar to a surgical wound. In another, they applied compressive force to simulate injuries from car accidents or severe falls.
Both approaches triggered hallmark features of spinal cord injury: cell death, inflammation and glial scarring. Glial scars form when astrocytes cluster tightly around damaged tissue. It created a dense physical and chemical barrier that prevents nerve regeneration.
“We could distinguish between astrocytes that are part of normal tissue and astrocytes in the glial scar, which are large and very densely packed,” Stupp said. “We also detected the production of chondroitin sulfate proteoglycans, molecules that respond to injury and disease.”
The ability to reproduce these effects in human tissue marks a turning point in spinal cord injury research, where much of the progress has historically relied on animal models.
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How ‘Dancing Molecules’ Work
After establishing the injury model, researchers applied a novel therapy developed in Stupp’s laboratory. Known as “dancing molecules,” the treatment consists of supramolecular therapeutic peptides that self-assemble into nanofibers when injected.
The therapy quickly transforms into a gel-like scaffold that mimics the spinal cord’s extracellular matrix. The nanofibers contain more than 100,000 molecules working together.
“Cells and their receptors are in constant motion,” Stupp explained. “You can imagine that molecules moving more rapidly would encounter these receptors more often. If the molecules are sluggish and not as ‘social,’ they may never come into contact with the cells.”
By increasing the collective motion of molecules within the nanofibers, the team found the therapy activated cell receptors more efficiently, promoting tissue repair.
The therapy previously showed huge results in animal studies. A single injection administered 24 hours after severe injury enabled paralyzed mice to regain walking ability within four weeks. The treatment recently received Orphan Drug Designation from the US Food and Drug Administration.
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Regeneration Observed in Human Tissue
When applied to injured organoids, the dancing molecules therapy significantly reduced inflammation and reduced the size of glial scar-like tissue. Researchers observed robust neurite outgrowth, long neuronal extensions that enable cells to communicate.
In spinal cord injuries, axons are often severed, breaking communication between the brain and body. This disconnection causes paralysis and loss of sensation beneath the injury.
After treatment, the organoids displayed organized neurite growth patterns resembling the regeneration previously observed in animal models.
“After applying our therapy, the glial scar faded significantly to become barely detectable,” Stupp said. “We saw neurites growing, resembling the axon regeneration we saw in animals. This validates that our therapy has a good chance of working in humans.”
Notably, before creating the injury model, the team tested the therapy on healthy organoids. The dancing molecules triggered dramatic neurite growth on the tissue surface, whereas less dynamic molecules produced no visible effect.
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“This difference was very vivid,” Stupp added.
The findings represent a major milestone in the treatment of paralysis. Researchers aim for human clinical trials. The organoid platform provides a critical bridge between animal research and patient studies.
The team plans to create even more sophisticated spinal cord organoids. The experiment includes models that simulate chronic injuries, which often involve more stubborn scar tissue. They also envision personalized medicine applications in which a patient’s own stem cells could generate implantable spinal tissue with a reduced risk of immune rejection.
The research was supported by Northwestern’s Center for Regenerative Nanomedicine. By combining advanced organoid technology with dynamic molecular therapies, scientists are moving closer to treatments that may restore mobility and independence to patients affected by devastating spinal injuries.
