Autoimmune and rheumatic diseases affect millions of people worldwide and can involve the joints, skin, gut, nervous system, and many other organs. Conditions like rheumatoid arthritis, osteoarthritis, lupus, inflammatory bowel disease, multiple sclerosis, and Sjögren’s syndrome often cause chronic pain, fatigue, and progressive damage.
Standard treatments usually focus on calming the immune system with medications such as steroids, immunosuppressants, or biologic drugs. While these can be effective, they often come with side effects, do not work for everyone, and rarely offer a true long-term cure.
Because of this, there is growing interest in therapies that can not only reduce inflammation but also help reset the immune system and support tissue repair.
Mesenchymal stem cells (MSCs) are among the most studied cell types in this field. An extensive new analysis of randomized controlled trials focused specifically on MSCs for autoimmune and rheumatic diseases to better answer two key questions: how well do they work, and how safe are they?
Understanding Mesenchymal Stem Cells and Their Role in Immune Disease
Mesenchymal stem cells are a type of adult stem cell that can be isolated from many tissues, including bone marrow, adipose tissue, umbilical cord, placenta, and dental pulp. They can renew themselves, form bone, cartilage, and fat cells under certain conditions, and, significantly, interact with the immune system.
MSCs have low expression of surface markers that typically trigger rejection, so they can often be used from a donor without provoking a strong immune response. They can also “sense” inflammatory signals and respond by releasing a range of anti-inflammatory and tissue-supporting molecules. These include cytokines, growth factors, and extracellular vesicles that can influence T cells, B cells, macrophages, dendritic cells, and other immune system influencers.
Because of these properties, MSCs are being studied as a way to calm overactive immune responses, promote immune tolerance, and support repair in tissues damaged by chronic inflammation. Researchers are exploring their potential as an add-on or alternative to traditional immunosuppressive therapies in many autoimmune and rheumatic conditions.
How the Study Was Conducted
To get a clearer picture of MSCs across diseases, Zeng et al. performed a systematic review and meta-analysis of randomized controlled trials. They searched major English and Chinese medical databases through December 2023 and identified 42 randomized controlled trials involving 2,183 participants.
These trials covered several autoimmune and rheumatic conditions, including rheumatoid arthritis, osteoarthritis, spondyloarthritis, systemic sclerosis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, and primary Sjögren’s syndrome.
The research team looked at how MSC therapy affected symptoms, disease activity scores, pain scales, and other clinical measures in each disease. They also carefully examined safety by comparing rates of adverse events, such as infections, worsening disease, and other complications, between MSC-treated patients and control groups.
Overall Findings: Promising Benefits in Some Diseases, Mixed Results in Others
The conclusion from this analysis is that MSC therapy shows encouraging benefits in several autoimmune and rheumatic diseases, while in others, the results are more modest or still unclear.
For osteoarthritis, MSC injections into the joint were associated with meaningful improvements in pain and function. Across multiple trials, patients who received MSCs from bone marrow, umbilical cord, or adipose tissue reported less pain on visual analog scales and better scores on standard osteoarthritis questionnaires, particularly in the adipose-derived MSC group. Stiffness did not consistently improve, but overall pain and function did.
In systemic lupus erythematosus, MSC therapy led to significant reductions in disease activity scores and improvements in kidney-related measures such as protein in the urine. Complement levels, which are often low in active lupus, improved in the MSC-treated group. These changes suggest a significant impact on the underlying immune activity, not just symptoms.
In inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, MSC therapy improved clinical response and remission rates compared to control treatments. This aligns with previous work showing benefits in challenging cases, such as complex perianal fistulas.
By contrast, in multiple sclerosis and systemic sclerosis, the meta-analysis did not show a clear improvement in key outcomes such as lesion number or disability scores for MS, or consistent, statistically strong benefits for SSc. That does not mean there is no benefit at all; it may reflect limited trial numbers, small sample sizes, or the need for more optimized treatment protocols.
For conditions like rheumatoid arthritis, spondyloarthritis, and primary Sjögren’s syndrome, the results are encouraging but still based on relatively few randomized trials. Early studies suggest improvements in pain, function, disease activity scores, and gland function, but larger, longer-term trials are needed.
Key Findings Across Individual Diseases
In patients with knee osteoarthritis, intra-articular MSC injections improved pain and physical function. Patients who received MSCs, especially from adipose tissue, reported better walking ability, reduced discomfort, and overall improved joint function. Although cartilage regeneration is still being actively studied, these results support MSCs as a potential tool for symptom relief and functional improvement.
In rheumatoid arthritis, a small number of trials showed that bone marrow–derived MSCs were well tolerated and associated with reduced disease activity, better joint symptoms, and meaningful response rates that lasted up to a year in many patients. Immunologic measures also shifted in a more favorable direction, with reduced inflammatory signals.
In spondyloarthritis, early data from a single randomized trial suggest possible improvement compared to a standard biologic treatment, but the evidence base is still very limited.
In systemic sclerosis, one trial using adipose-derived regenerative cells suggested some improvement in hand function and disability scores in patients with diffuse cutaneous disease, especially over longer follow-up, but not all results reached statistical significance.
In primary Sjögren’s syndrome, MSC therapy improved dryness symptoms, salivary and tear gland function, and reduced disease activity scores in the trial included in this review. Laboratory markers such as immunoglobulin levels and inflammatory markers also improved.
In systemic lupus erythematosus, MSCs reduced disease activity and improved kidney involvement, while maintaining a safety profile similar to standard therapy.
In inflammatory bowel disease, MSC therapy improved clinical efficacy without raising the rate of adverse events, supporting its role as a potential option, particularly in complex or treatment-resistant cases.
In multiple sclerosis, MSC therapy did not significantly improve lesion counts, lesion volume, or disability scores in the combined analysis of randomized trials. However, many early-phase, non-randomized studies still support the safety of MSCs and suggest potential benefits that need confirmation in better-designed, larger trials.
Safety Findings: No Increase in Adverse Events
One of the most important questions for any new therapy is safety. In this extensive review, MSC transplantation did not increase the risk of adverse events in the conditions studied.
For osteoarthritis, lupus, inflammatory bowel disease, and multiple sclerosis, the rates of adverse events were similar between MSC-treated patients and control groups. In other words, adding MSC therapy did not make side effects more common. Notably, there was no signal that MSCs increased serious risks such as infections, malignancy, or severe treatment-related complications across these trials.
This supports the idea that MSC therapy, when prepared and administered under appropriate clinical protocols, has a favorable safety profile in autoimmune and rheumatic diseases. However, as with any treatment, patients should be monitored carefully, and long-term follow-up remains essential.
Immune Regulation by MSCs in Autoimmune and Rheumatic Disease
Although each disease is different, many autoimmune and rheumatic disorders share a common theme: the immune system loses tolerance and begins attacking the body’s own tissues. MSCs seem to help by gently “rebalancing” the immune system rather than shutting it down completely.
MSCs can reduce overactive T and B cell responses, promote regulatory T cells that help maintain tolerance, and shift inflammatory cells toward more calming, tissue-protective roles. They also release factors that support tissue repair, improve the local microenvironment, and influence pathways involved in healing and regeneration.
This multi-layered action may explain why MSCs show promise across different diseases that all have an immune and inflammatory component, even though the specific organs affected are not the same.
Remaining Challenges and Future Directions
Despite promising signals, the authors of the review emphasize that MSC therapy is not a one-size-fits-all solution and that there is still work to be done. Different studies used different cell sources, doses, timing, and treatment schedules. These differences likely contribute to the variation in results.
The researchers also suggest that MSCs are most likely to be effective when combined with other treatments rather than used alone, that early intervention may be more beneficial than late-stage treatment, and that multiple doses may be more effective than a single infusion in some cases. They also stress the importance of tailoring protocols to the specific disease and patient rather than applying a rigid standard formula.
Larger, high-quality randomized controlled trials are still needed, especially in conditions like rheumatoid arthritis, spondyloarthritis, systemic sclerosis, multiple sclerosis, and primary Sjögren’s syndrome, where early results are promising but not yet definitive.
What These Findings Mean for Patients
For patients and families living with autoimmune or rheumatic immune diseases, this analysis offers cautious optimism. The evidence suggests that mesenchymal stem cell transplantation may help reduce symptoms and disease activity in several conditions, especially osteoarthritis, systemic lupus erythematosus, inflammatory bowel disease, and primary Sjögren’s syndrome, with encouraging signals in rheumatoid arthritis and some others.
Just as importantly, MSC therapy appears to have a favorable safety profile in the clinical trials analyzed, with no increase in overall adverse events compared to standard treatments or placebo.
However, MSC therapy is still being actively studied, and it is not yet a universally established standard of care for these diseases.
As research continues, the goal is to refine MSC-based treatments so they are safer, more consistent, and more effective, helping address the unmet needs of people living with chronic autoimmune and rheumatic diseases.
Source: Zeng, L., Liu, C., Wu, Y. et al. Efficacy and safety of mesenchymal stromal cell transplantation in the treatment of autoimmune and rheumatic immune diseases: a systematic review and meta-analysis of randomized controlled trials. Stem Cell Res Ther 16, 65 (2025). https://doi.org/10.1186/s13287-025-04184-x
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