US researchers have developed a human spinal cord organoid model that reproduces injury responses and could speed regenerative therapies.
Organoids are mini versions of organs grown from stem cells that mimic real tissue structure and function.
For the first time, the model accurately replicated cell death, inflammation and glial scarring, a dense barrier that blocks nerve regrowth.
The study was carried out by researchers at Northwestern University.
Using injured human spinal cord organoids, they tested “dancing molecules”, a therapy previously shown in animals to reverse paralysis and repair tissue.
Treated organoids showed significant neurite outgrowth, the long projections that connect nerve cells, and the scar-like tissue diminished.
The therapy, introduced in 2021, uses molecular motion to repair traumatic spinal cord injury.
Injected as a liquid, it gels into a network of nanofibres that imitates the extracellular matrix, the natural scaffold around spinal cord cells. Fine-tuning the molecules’ collective motion improves their engagement with cell receptors.
In mice, a single injection given 24 hours after severe injury helped the animals walk again within four weeks.
Samuel I. Stupp, the study’s senior author and inventor of the therapy, said: “One of the most exciting aspects of organoids is that we can use them to test new therapies in human tissue.
“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.”
To model spinal cord injury, the team created two common injuries: a laceration (with a scalpel) and a compressive contusion, similar to damage from a serious crash or fall. Both caused cell death and glial scar formation, as seen in real injuries.
They also added microglia, the brain’s immune cells, to simulate inflammatory responses.
Stupp said: “We were the first to introduce microglia into a human spinal cord organoid, so that was a huge accomplishment.
“It means that our organoid has all the chemicals that the resident immune system produces in response to an injury. That makes it a more realistic, accurate model of spinal cord injury.”
Applied to injured organoids, the liquid therapy gelled to form a scaffold, calmed inflammation, reduced scarring, extended neurites and encouraged orderly nerve growth.
In spinal cord injury, axons (a type of neurite) are often severed, disrupting nerve communication and causing paralysis; regenerating these projections could help restore function.
Stupp links the success to supramolecular motion, the ability of molecules to move rapidly or briefly leave the nanofibres.
“Before we even developed the injury model, we tested the therapy on a healthy organoid,” he said.
“The dancing molecules spun out all these long neurites on the surface of the organoid but, when we used molecules that had less or no motion, we saw nothing. This difference was very vivid.”
The therapy has Orphan Drug Designation from the US Food and Drug Administration.
Next, the team plans more advanced organoids, including models of chronic injury with tougher scar tissue, and ultimately personalised implants grown from a patient’s own stem cells to avoid immune rejection.
