Spinal cord injury (SCI) is a life-changing condition that affects hundreds of thousands of people in the United States. Each year, approximately 17,000 new cases are reported, and more than 290,000 individuals are living with long-term effects. Damage to the spinal cord can lead to partial or complete loss of movement and sensation below the level of injury. Beyond the physical impact, SCI can also bring significant emotional, social, and financial challenges.
Current treatment options for people with subacute or chronic SCI mainly focus on managing symptoms and maximizing function through rehabilitation. While physical therapy, assistive devices, and medical management can improve quality of life, they do not repair the damaged spinal cord. This reality has led researchers to explore regenerative medicine approaches, such as stem cell therapy, as potential ways to support healing and recovery.
Understanding Adipose-Derived Mesenchymal Stem Cells
Among the many types of stem cells being studied, mesenchymal stem cells (MSCs) have received considerable attention. These cells are found in several tissues of the body, including bone marrow and fat. Fat tissue, also known as adipose tissue, is an especially rich and accessible source. Stem cells collected from fat are called adipose-derived mesenchymal stem cells, or AD-MSCs.
AD-MSCs are appealing for several reasons. They are relatively easy to obtain through a minimally invasive procedure, can be expanded in the laboratory to reach higher numbers, and can develop into multiple types of cells. In addition, research suggests they may help regulate inflammation, promote blood vessel formation, and support nerve repair. Animal studies of spinal cord injury have shown that AD-MSCs can create a more favorable environment for healing by calming harmful inflammation and encouraging regenerative processes.
Encouraged by promising preclinical findings and early case reports, researchers launched a Phase I clinical trial known as CELLTOP to evaluate the safety and feasibility of using AD-MSCs in people with traumatic spinal cord injury.
Design of the CELLTOP Phase I Trial
The CELLTOP study was registered on ClinicalTrials.gov (NCT03308565) and designed primarily to assess safety.
The trial included ten patients who had sustained traumatic spinal cord injuries and were classified as American Spinal Injury Association Impairment Scale (AIS) grade A or B at the time of injury. The AIS scale is commonly used to describe the severity of spinal cord injury. Grade A represents a complete injury with no motor or sensory function preserved below the level of injury. Grade B indicates some preserved sensation but no motor function below the injury level.
For each participant, fat tissue was collected and processed in a laboratory to culture and expand the patient’s own stem cells. A dose of 100 million cells was prepared for each individual. These cells were then delivered intrathecally, meaning they were injected into the cerebrospinal fluid surrounding the spinal cord. All ten patients successfully underwent stem cell harvesting, cell manufacturing, and intrathecal administration.
The primary outcome of the study was safety, measured by tracking adverse events. Secondary outcomes included changes in motor and sensory function, imaging findings, cerebrospinal fluid markers, and somatosensory evoked potentials. Patients were followed for up to 96 weeks after treatment.
Safety Results and Tolerability
The study met its primary goal of demonstrating safety. No serious adverse events were reported during the study period. This finding is important because it suggests that harvesting and delivering autologous AD-MSCs into the spinal fluid can be performed without major complications in carefully selected patients.
However, non-serious adverse events were common. The most frequently reported issues were headache and musculoskeletal pain, experienced by eight of the ten participants. These symptoms were considered manageable and did not lead to withdrawal from the study.
Imaging studies showed that several patients developed changes, including thickening or clumping of nerve roots in the lower spine. Similar findings have been reported in other studies of intrathecal stem cell administration. While some case reports in the literature have suggested that these imaging changes may be linked to inflammation or nerve root compression, the patients in this study did not exhibit corresponding neurological deterioration. The MRI findings did not appear to be associated with new or worsening symptoms. Researchers have proposed that these changes may represent a reactive or inflammatory response to the infusion rather than harmful damage. Further research is needed to better understand the significance of these imaging findings.
Early Signals of Neurological Improvement
Although safety was the main focus, the researchers also monitored neurological function. At the final follow-up, 7 of the 10 patients showed improvement in their AIS grade compared with their status at the time of injection. Several participants demonstrated gains in motor and sensory function.
Notably, among the five patients who were classified as AIS grade A at the time of injection, two improved to grade C by the end of follow-up. This level of improvement after a period of neurological plateau is encouraging. However, these results must be interpreted with caution.
Phase I trials are small and do not include a control group. Without a comparison group, it is not possible to determine whether improvements were due to the stem cell treatment, ongoing rehabilitation, natural recovery, or a combination of factors. Previous research has shown that a small percentage of patients with severe spinal cord injury can experience late neurological improvement even without experimental treatment. Therefore, larger randomized controlled trials are needed to confirm whether AD-MSC therapy truly contributes to functional recovery.
Potential Mechanisms of Action
Researchers believe that the benefits of mesenchymal stem cells may not come from directly replacing damaged nerve cells. Instead, MSCs appear to work through paracrine effects. This means they release signaling molecules that influence surrounding tissues. These molecules can help regulate inflammation, promote blood vessel formation, and support the body’s own repair processes.
In this study, investigators observed increased levels of vascular endothelial growth factor (VEGF) in the cerebrospinal fluid after treatment. VEGF plays a role in forming new blood vessels and may contribute to improved tissue repair. While this finding supports the idea that AD-MSCs may act through paracrine mechanisms, more research is needed to better understand the complex biological processes involved. Future studies may expand the range of inflammatory and immune markers measured to provide a more detailed picture of how these cells influence the injured spinal cord.
Looking Ahead
The CELLTOP Phase I trial provides important early evidence that intrathecal administration of autologous adipose-derived mesenchymal stem cells is feasible and well tolerated in patients with traumatic spinal cord injury. No serious adverse events were reported, and most patients experienced some degree of neurological improvement over nearly two years of follow-up.
However, these findings represent only the first step in clinical development. The small sample size and lack of a control group limit conclusions about effectiveness. Larger, well-designed randomized controlled trials are essential to determine whether AD-MSC therapy can meaningfully improve long-term outcomes for people living with spinal cord injury.
While more research is needed, studies like CELLTOP help build the scientific foundation for future therapies aimed at restoring function and improving quality of life.
Source: Bydon, M., Qu, W., Moinuddin, F.M. et al. Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial. Nat Commun 15, 2201 (2024). https://doi.org/10.1038/s41467-024-46259-y