Low-Dose Mesenchymal Stem Cell Therapy for Discogenic Pain: Current Evidence, Safety Considerations, and Clinical Implications

by admin | Sep 11, 2025 | Mesenchymal Stem Cells, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy, Studies

Low back pain (LBP) is one of the most common health problems worldwide, affecting nearly 60 to 80 percent of adults at some point in their lives. It’s the second most frequent reason people visit a doctor and one of the leading causes of work disability. For many, the costs aren’t just personal—they include substantial healthcare expenses and lost productivity. A large portion of chronic low back pain is linked to problems with the intervertebral discs, the soft cushions that sit between the vertebrae. When these discs degenerate, they can lose height, dry out, and develop tears, leading to persistent pain and reduced function.

Traditionally, people with disc-related LBP have relied on a mix of pain medications, physical therapy, and sometimes surgery. While these approaches can help, they often provide only temporary relief and may come with unwanted side effects. Medications, especially opioids, can lead to dependency or other complications. Physical therapy offers modest benefits for many, and surgeries like discectomy or spinal fusion have inconsistent outcomes and may involve long recovery periods. 

This study provides initial evidence of the safety and efficacy of low-dose autologous adipose-derived mesenchymal stem cells (ADMSCs) for discogenic LBP.

Mesenchymal Stem Cells and Disc Regeneration

Stem cells, particularly mesenchymal stem cells (MSCs), have gained attention for their ability to support tissue repair. MSCs can be obtained from several sources, including bone marrow, umbilical cord tissue, and fat (adipose tissue). They release growth factors, cytokines, and other molecules that can reduce inflammation, prevent cell death, and stimulate the body’s natural repair processes. Rather than becoming new disc cells themselves, MSCs create an environment that promotes healing within the damaged disc.

Bone marrow-derived MSCs were some of the first to be studied for disc degeneration, but harvesting them can be painful and yield relatively few stem cells. Adipose tissue, by contrast, provides an abundant source of MSCs that are easier to collect and expand for therapy. Early research using bone marrow and adipose-derived MSCs has shown promise in improving pain and function in people with disc-related low back pain. However, questions remained about the safety of these treatments and whether lower doses of adipose-derived stem cells could still be effective.

The Study: Testing Low-Dose Adipose-Derived MSCs

This study by Bates et al. aimed to evaluate the safety and effectiveness of low-dose autologous adipose-derived mesenchymal stem cells (ADMSCs) for the treatment of discogenic low back pain. “Autologous” means that the stem cells come from the patient’s own body, reducing the risk of rejection or other immune reactions. The study included nine participants with chronic low back pain caused by degeneration of a single lumbar disc.

Each participant received an intradiscal injection of 10 million ADMSCs, with the option to repeat the injection six months later if needed. Over the following year, participants were closely monitored for any adverse effects and changes in pain, function, and quality of life. MRI scans were also used to examine the discs themselves.

Safety and Tolerability of ADMSC Injections

One of the most important findings from this study was safety. None of the participants experienced unexpected or serious adverse events related to the treatment. Only one participant experienced a temporary flare in pain after the injection, which was managed with standard pain medications. Overall, the procedure was well tolerated and demonstrated a strong safety profile, which is critical for any new therapy.

Pain Relief and Functional Improvements

The majority of participants reported meaningful improvements in their pain levels. After 12 months, seven out of nine participants (78%) reported reductions in average pain, and six participants (67%) reported improvements in their most severe pain episodes. Clinically significant improvements—those that made a real difference in daily life—were observed in most participants.

Functionally, the benefits were clear as well. Five participants (56%) reported being able to work more effectively, and three participants were able to reduce their use of pain medications. Measures of quality of life, including the ability to perform daily activities and self-care, also improved for most participants. Importantly, none of the participants reported any worsening of their condition during the study period.

MRI Findings and Disc Health

MRI scans at 12 months showed that the treated discs remained stable. There was no further loss of disc height or progression of degenerative changes in the vertebrae. In some cases, annular fissures—the tears in the outer layer of the disc—had partially or fully healed. Two participants also showed a reduction in disc protrusion, in which part of the disc protrudes outward. While it’s unclear whether these changes were directly caused by the stem cell therapy or natural healing processes, the stabilization of the discs was a positive finding.

Who Benefits Most?

Interestingly, the study suggested that certain characteristics might predict better outcomes. Participants with Modic type 2 changes (a type of vertebral bone change seen on MRI) and no annular tears seemed to respond particularly well. Those with annular tears or other types of changes did not experience as much benefit. While the study was small, this finding suggests the potential for more targeted treatment in the future, in which patients are selected based on specific disc characteristics.

Comparing Stem Cell Therapy to Traditional Treatments

Compared to conventional approaches, stem cell therapy offers several potential advantages. Medications, particularly opioids, provide limited relief and carry significant risks. Physical therapy can be helpful, but improvements are usually modest. Surgical interventions can be effective for severe cases, but they are invasive, carry risks, and often require long recovery periods. Stem cell therapy, by contrast, is minimally invasive and may offer both pain relief and functional improvements, with a strong safety profile.

Other studies have explored similar approaches, using higher doses of MSCs or combining them with carriers such as hyaluronic acid. This study’s use of a lower dose in a simple isotonic solution is significant because it shows that even a relatively small number of stem cells can produce meaningful results without additional substances. This could make treatment faster, simpler, and more cost-effective.

Limitations and Considerations

While the results are promising, it’s important to recognize the study’s limitations. The sample size was small, and there was no control group, so it’s difficult to make definitive conclusions about efficacy. The study also excluded participants with more severe or multi-level disc degeneration, so the findings may not apply to all patients with chronic low back pain.

Another consideration is the variability in response. Not all participants experienced the same level of benefit, and some improvements were modest. The timing of additional doses may also matter; in this study, those who did not achieve significant improvement after six months generally did not see large gains at 12 months, even with a second injection.

The Potential of ADMSC Therapy

Despite these limitations, the study provides encouraging evidence that low-dose ADMSC therapy is safe and has the potential to reduce pain and improve function in people with discogenic low back pain. The therapy was well-tolerated, and most participants experienced meaningful improvements in pain, daily function, and quality of life. MRI results also suggested that disc health could be maintained or even partially restored.

For patients with specific characteristics, such as Modic type 2 changes without annular tears, stem cell therapy may be particularly beneficial. Future studies with larger participant groups, control arms, and longer follow-up will help to confirm these findings and better define which patients are most likely to benefit.

Clinical Implications and Future Directions for ADMSC Therapy in Discogenic Low Back Pain

Chronic low back pain remains a challenging condition with limited effective treatments. Current approaches, including medication, physical therapy, and surgery, often provide only partial relief and can come with significant risks. Stem cell therapy, particularly using adipose-derived mesenchymal stem cells, offers a new avenue for treating discogenic pain.

This study demonstrated that low-dose ADMSC injections are safe and well tolerated, and are associated with meaningful improvements in pain, function, and quality of life for most participants. MRI scans suggested stabilization and partial healing of the discs, and certain patient characteristics may help predict who will benefit most.

While more research is needed, the findings are promising. Stem cell therapy could become a valuable treatment option for patients with discogenic low back pain, offering relief without the risks and limitations of traditional approaches. For individuals struggling with chronic disc-related pain, ADMSC therapy represents a potential step toward better function, less pain, and improved quality of life.

Source: Bates D, Vivian D, Freitag J, Wickham J, Mitchell B, Verrills P, Shah K, Boyd R, Federman D, Barnard A, O’Connor L, Young JF. Low-dose mesenchymal stem cell therapy for discogenic pain: safety and efficacy results from a 1-year feasibility study. Future Sci OA. 2022 Apr 21;8(5):FSO794. doi: 10.2144/fsoa-2021-0155. PMID: 35662742; PMCID: PMC9136638.

Understanding the Safety of Mesenchymal Stromal Cell Therapy

by admin | Sep 2, 2025 | Mesenchymal Stem Cells, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy, Studies

Mesenchymal stromal cell therapy, often called MSC therapy, has become one of the most widely studied approaches in regenerative and cellular medicine. Over the past two decades, researchers have explored its potential to treat a wide range of inflammatory and immune-related conditions, including heart disease, lung injury, autoimmune disorders, and complications following cancer treatment.

As interest grows and more patients are invited to participate in clinical trials, one question becomes increasingly important: Is MSC therapy safe? This large, updated scientific review provides reassuring answers, demonstrating that MSC therapy continues to show a strong, favorable safety profile across thousands of patients and dozens of high-quality clinical trials.

As part of this review, Thompson et al. explain what MSC therapy is, why safety is such a critical concern, how researchers evaluated safety across many studies, and what the findings mean for patients, families, clinicians, and regulators.

Mesenchymal Stromal Cells and Their Therapeutic Role

Mesenchymal stromal cells are multipotent cells that can be collected from adult tissues such as bone marrow, adipose tissue, and other sources. They were first described in the 1970s and have since gained attention for their ability to interact with the immune system and respond to inflammation.

Unlike embryonic stem cells, MSCs have a limited ability to turn into different cell types. Instead, their primary therapeutic value appears to lie in their ability to communicate with surrounding tissues. MSCs release bioactive molecules that help regulate immune responses, reduce excessive inflammation, and promote healing. They also migrate toward areas of injury or inflammation, making them attractive candidates for conditions where inflammation plays a central role.

Preclinical research, including animal studies, has shown promising results in conditions such as acute lung injury, sepsis, and heart attack. These findings have led to a growing number of human clinical trials evaluating both safety and potential benefits.

Safety Considerations for Mesenchymal Stromal Cell Therapy

Any therapy that involves living cells raises important safety questions. MSCs can divide, interact with the immune system, and circulate through the bloodstream. Because of these properties, scientists carefully monitor potential risks that could limit clinical use.

Early clinical trials suggested MSCs were generally safe, but these studies were small. As more trials were completed and patient numbers increased, researchers recognized the need to systematically review the evidence to identify any consistent safety signals that might not be obvious in individual studies.

Methods Used to Evaluate MSC Safety

To answer this question, researchers conducted a comprehensive systematic review and meta-analysis of randomized controlled trials. These trials compared patients who received MSC therapy via the bloodstream with those who received standard care or a placebo.

The review included studies published between 2012 and 2019 and built on an earlier 2012 review. The authors searched major medical databases and screened nearly 7,500 scientific papers. After careful evaluation, 55 randomized controlled trials involving 2,696 adult patients met the inclusion criteria.

By pooling data from multiple trials and using rigorous statistical methods, the researchers were able to estimate whether MSC therapy increased the risk of any negative events compared to control treatments.

Incidence of Fever Following MSC Therapy

Across all included trials, fever was the only adverse event that occurred more frequently in patients receiving MSC therapy compared to controls. Patients treated with MSCs were about 2.5 times more likely to develop a fever.

Notably, most of these fevers were mild and temporary. Although some fevers were reported as serious adverse events, they were rare overall. Fever typically occurred shortly after infusion and resolved without long-term consequences.

This finding is consistent with earlier reviews and is thought to reflect the body’s immune response to the infused cells rather than a sign of lasting harm. Recognizing fever as a known and manageable side effect helps clinicians monitor patients appropriately during and after treatment.

No Increased Risk of Infection, Thrombosis, or Malignancy

Beyond fever, the review found no significant increase in other major safety concerns. Patients receiving MSC therapy did not experience higher infection rates than controls, despite the cells’ immune-modulating effects. This suggests that MSCs do not meaningfully weaken immune defenses in clinical settings.

The analysis also found no association between MSC therapy and thrombotic or embolic events. Blood clots were rare overall and occurred at similar rates in both MSC-treated patients and control groups. This is particularly reassuring given ongoing research into how MSCs may interact with clotting pathways.

Perhaps most importantly, the review found no increased risk of malignancy. MSC-treated patients did not develop cancer more frequently than those in control groups. This finding addresses a longstanding concern related to the cells’ ability to proliferate and supports their continued investigation in clinical medicine.

Observed Reduction in Mortality

One of the more notable findings from this review was a reduced risk of death in patients receiving MSC therapy compared to controls. While this review was focused on safety rather than effectiveness, this observation suggests that MSC therapy does not increase mortality risk and may even offer protective benefits in specific patient populations.

It is important to interpret this finding cautiously, as the trials involved varied conditions and were not designed to measure survival as a primary outcome. Still, the absence of increased mortality provides further reassurance regarding safety.

Improved Safety Monitoring in Recent Trials

Compared to earlier studies, recent MSC clinical trials demonstrated improved attention to safety monitoring. More than three-quarters of the included trials reported having a predefined plan to track adverse events, a substantial improvement over earlier research.

Notably, none of the trials were stopped early due to safety concerns. Serious adverse events that were judged to be related or possibly related to treatment were extremely rare, occurring in only a small fraction of patients across all studies.

This progress reflects a maturing field that recognizes the importance of transparency, standardized reporting, and rigorous trial design.

Challenges in Trial Design and Reporting

Despite these encouraging findings, the authors highlighted areas that still need improvement. Only a small number of trials met all criteria for low risk of bias, indicating that study design quality varies widely across the field.

Reporting of MSC characteristics was another area of concern. Only a minority of trials fully described how MSCs were defined, tested for viability, or assessed for biological potency. These details are critical for understanding why some trials succeed while others do not.

Without consistent reporting standards, it becomes harder to compare results across studies or identify factors that influence outcomes. Improving transparency in cell characterization will be essential as newer, second-generation MSC products move into clinical trials.

Implications for Patients and Families

For patients considering participation in MSC clinical trials or learning about regenerative medicine options, this large body of evidence offers important reassurance. Across thousands of patients and dozens of trials, MSC therapy has consistently shown a strong safety record.

The most common side effect, fever, is generally temporary and manageable. Serious concerns such as infection, blood clots, cancer, and death have not been linked to MSC therapy when compared to standard treatments.

As with any investigational therapy, participation in clinical trials should involve careful discussion with healthcare providers, but concerns about safety alone should not be a barrier, given the current evidence.

Future Directions in MSC Research

MSC research continues to evolve as researchers learn more about how these cells work, how they interact with the immune and clotting systems, and how manufacturing methods influence their behavior. Future trials will explore new indications, refined dosing strategies, and enhanced cell products designed to improve consistency and effectiveness.

Ongoing safety monitoring remains essential, particularly as therapies move into larger and more diverse patient populations. Continued adherence to rigorous trial design and transparent reporting will help ensure that advances in regenerative medicine are both effective and safe.

Overall Conclusions on MSC Safety

Thompson et al.’s updated review provides the most comprehensive evaluation to date of the safety of mesenchymal stromal cell therapy in adult clinical trials. Aside from an increased likelihood of fever, no meaningful safety signals were identified across thousands of patients.

The findings reinforce the conclusion that MSC therapy continues to demonstrate a favorable safety profile. For researchers, clinicians, regulators, and patients alike, this growing body of evidence supports the responsible, ongoing development of MSC-based therapies as part of the evolving field of regenerative medicine.

As research progresses, maintaining high standards for study design, cell characterization, and adverse event reporting will be key to translating this promising therapy into broader clinical practice.



Source: Thompson M, Mei SHJ, Wolfe D, Champagne J, Fergusson D, Stewart DJ, Sullivan KJ, Doxtator E, Lalu M, English SW, Granton J, Hutton B, Marshall J, Maybee A, Walley KR, Santos CD, Winston B, McIntyre L. Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: An updated systematic review and meta-analysis. EClinicalMedicine. 2020 Jan 17;19:100249. doi: 10.1016/j.eclinm.2019.100249. PMID: 31989101; PMCID: PMC6970160.