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.
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