Lab grown human spinal cord heals after injury in major breakthrough

In the new research, the team worked with human spinal cord organoids — miniature organs derived from stem cells — to recreate different forms of spinal cord trauma and evaluate a promising regenerative treatment.

For the first time, researchers showed that these human spinal cord organoids can faithfully reproduce the major biological consequences of spinal cord injury. The model displayed cell death, inflammation, and glial scarring, which is a thick buildup of scar tissue that forms a physical and chemical barrier preventing nerve repair.

When the damaged organoids were treated with “dancing molecules” — a therapy that restored movement and repaired tissue in a previous animal study — the results were dramatic. The injured tissue produced substantial neurite outgrowth, meaning the long extensions that allow neurons to communicate began growing again. Scar like tissue was greatly reduced. The findings add support to the idea that this therapy, which recently received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA), could improve recovery for people with spinal cord injuries.

The study was published on Feb. 11 in Nature Biomedical Engineering.

“One of the most exciting aspects of organoids is that we can use them to test new therapies in human tissue,” said Northwestern’s Samuel I. Stupp, the study’s senior author and inventor of dancing molecules. “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.”

Stupp is a leader in regenerative materials science and holds the title of Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering at Northwestern. He has appointments in the McCormick School of Engineering, Weinberg College of Arts and Sciences and Feinberg School of Medicine, and directs the Center for Regenerative Nanomedicine (CRN). The paper’s first author is Nozomu Takata, a research assistant professor of medicine at Feinberg and member of CRN.

Why Human Organoids Matter

Organoids are grown from induced pluripotent stem cells in the laboratory. Although they are simplified versions of full organs, they closely resemble real tissue in structure, cellular diversity, and function. Because of this, organoids are powerful tools for studying disease, testing treatments, and exploring how organs develop. They also allow researchers to move faster and at lower cost compared to animal experiments or human clinical trials.

While other groups have produced spinal cord organoids to study basic biology, this model represents a major advance for injury research. The organoids measured several millimeters across and were mature enough to sustain and model traumatic damage.

Over several months, the team guided stem cells to form complex spinal cord tissue containing neurons and astrocytes. They also became the first to incorporate microglia — immune cells found in the central nervous system — to better replicate the inflammatory response that follows spinal cord injury.

“It’s kind of a pseudo-organ,” 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.”

What Are Dancing Molecules

Once the spinal cord organoids were fully developed, the researchers turned their attention to testing injury and treatment. First introduced in 2021, the dancing molecules therapy uses controlled molecular motion to repair tissue and potentially reverse paralysis after traumatic spinal cord injury. It belongs to a broader class of supramolecular therapeutic peptides (STPs), which rely on large assemblies of 100,000 or more molecules to activate cell receptors and stimulate the body’s natural repair signals. (The concept of supramolecular therapies also is used in current GLP-1 drugs for weight loss and diabetes, an area that Stupp’s lab investigated nearly 15 years ago.)

The therapy is delivered as a liquid injection that quickly forms a web of nanofibers resembling the spinal cord’s extracellular matrix. By adjusting how dynamically the molecules move within this structure, researchers improved how effectively they interact with constantly shifting cell receptors.

“Given that cells themselves and their receptors are in constant motion, you can imagine that molecules moving more rapidly would encounter these receptors more often,” Stupp said in 2021. “If the molecules are sluggish and not as ‘social,’ they may never come into contact with the cells.”

In previous animal experiments, a single injection given 24 hours after a severe injury enabled mice to walk again within four weeks. Formulations with faster molecular motion performed better than slower versions, suggesting that increased movement enhances bioactivity and cellular signaling.

Simulating Spinal Cord Trauma

To test the therapy, the researchers created two common types of spinal cord injury in the organoids. Some were cut with a scalpel to mimic a laceration similar to a surgical wound. Others were subjected to a compressive contusion injury, comparable to trauma from a serious car crash or fall.

Both types of injury led to cell death and the formation of glial scars — just as occurs in real spinal cord injury.

“We could distinguish between the astrocytes that are a part of normal tissue and the astrocytes in the glial scar, which are large and very densely packed,” Stupp said. “We also detected the production of chondroitin sulfate proteoglycans, which are molecules in the nervous system that respond to injury and disease.”

After treatment with dancing molecules, the gelled nanofiber scaffold reduced inflammation, shrank glial scarring, stimulated neurite extension, and encouraged neurons to grow in organized patterns.

Neurites include axons, which are often severed in spinal cord injuries. When axons are cut, communication between neurons is disrupted, leading to paralysis and loss of sensation below the injury site. Promoting neurite regrowth could reconnect these pathways and help restore function.

The Role of Molecular Motion

Stupp credits the therapy’s effectiveness to supramolecular motion, meaning the ability of the molecules to move rapidly and even briefly detach from the nanofiber network. Experiments on healthy organoids reinforced this idea.

“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.”

Looking ahead, the team plans to engineer even more advanced organoids to refine their models. They also intend to develop versions that replicate chronic, long standing injuries, which typically involve thicker and more persistent scar tissue. With further development, Stupp said these miniature spinal cords could contribute to personalized medicine by generating implantable tissue from a patient’s own stem cells, reducing the risk of immune rejection.

The study, “Injury and therapy in a human spinal cord organoid,” was supported by the Center for Regenerative Nanomedicine at Northwestern University and a gift from the John Potocsnak Family for spinal cord injury research.