Every year, World Rheumatic Disease Day raises awareness about chronic autoimmune conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis, and Sjögren’s syndrome. These conditions not only affect joints and connective tissues but can also damage internal organs, causing significant pain and disability that impair quality of life. While modern immunotherapies and biologic drugs have improved disease control, many patients still struggle with refractory disease or experience long-term side effects from continuous medication use.
Science, Awareness, and Hope for Patients with Rheumatic Diseases
In recent years, stem cell therapy has emerged as one of the most promising frontiers in rheumatology. Among the various types of stem cells, mesenchymal stem/stromal cells (MSCs) derived from bone marrow, adipose tissue, or umbilical cord, have attracted strong scientific interest for their unique ability to modulate immune responses and promote tissue regeneration, offering new hope for patients whose conditions remain resistant to conventional treatments [1].
What Makes MSCs Special?
Unlike traditional treatments that simply suppress immune activity, MSCs act as biological modulators, helping the immune system restore balance [2]. They can:
- Promote regulatory T cells (Tregs) while suppressing autoreactive T and B cells.
- Secrete anti-inflammatory cytokines and growth factors that reduce inflammation.
- Release extracellular vesicles (exosomes) carrying molecular signals that calm immune attacks and encourage tissue repair
This dual mechanism, immunomodulation and regeneration enables MSCs to address both the underlying immune dysfunction and the tissue damage seen in rheumatic diseases, something conventional therapies rarely achieve.
Clinical Evidence: From Bench to Bedside
A 2025 systematic review and meta-analysis encompassing 42 randomized controlled trials and more than 2,000 patients with RA, SLE, systemic sclerosis, and Sjögren’s syndrome concluded that MSC therapy significantly improves disease activity and inflammatory markers, with an overall favorable safety profile [3]. These findings reinforce a growing body of clinical evidence demonstrating real-world benefit for patients with autoimmune rheumatic conditions.
-
Rheumatoid Arthritis
In RA, MSC infusions have been associated with notable reductions in Disease Activity Score (DAS28), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). A 2023 meta-analysis confirmed these outcomes, showing that improvements typically appear within the first 6–12 months post-treatment, although repeated administrations may be necessary to sustain remission [4].
-
Systemic Lupus Erythematosus
In SLE, several early-phase clinical studies have evaluated umbilical cord-derived MSCs (UC-MSCs) in refractory cases. A Phase I UC-MSC trial (NCT03171194) demonstrated excellent safety and favorable immunologic shifts notably, increases in regulatory immune cells and reductions in disease activity. Moreover, multiple clinical trials have reported significant reductions in proteinuria, autoantibody levels, and SLE Disease Activity Index (SLEDAI) among patients with lupus nephritis [5]. Ongoing studies such as MiSLE (NCT02633163) and NCT06485648 aim to confirm the long-term efficacy and safety of UC-MSC therapy in refractory lupus [6]. In addition, hematopoietic stem cell transplantation (HSCT) has been explored in severe, treatment-resistant SLE, offering another promising avenue for immune system reconstitution [7].
-
Other Rheumatic Diseases
Encouraging results have also been seen in systemic sclerosis, where MSCs appear to reduce skin fibrosis and enhance vascular repair. Early studies and compassionate-use cases report improved skin scores, microcirculation, and hand mobility [1]. In primary Sjögren’s syndrome, MSC therapy has shown the ability to restore salivary gland function and relieve dryness, possibly through the modulation of local immune activity [6]. Collectively, these studies highlight the broad therapeutic potential of MSCs across the rheumatic disease spectrum, positioning stem cell therapy as one of the most exciting and evolving strategies for autoimmune regulation and tissue restoration.
Safety, Challenges and Stemwell’s Role
Across hundreds of treated patients worldwide, MSC therapy has demonstrated an excellent safety record, with no serious adverse events such as malignancy or severe infection reported [3]. At Stemwell, we apply rigorous safety and quality standards to ensure that every patient receives MSC therapy under controlled, clinically validated conditions. However, as with any emerging therapy, several challenges remain:
- Variability, MSCs differ by tissue source, donor age, and cell culture methods.
- Standardization, Optimal dosing, delivery routes, and manufacturing protocols are not yet fully established.
- Durability, some patients show transient benefits, suggesting that booster infusions or combination approaches may be necessary.
- Mechanistic Clarity, Further research is needed to understand how MSCs persist in the body and influence immune memory [4].
Importantly, patients should seek treatment only through regulated clinical trials or approved research programs like those conducted at Stemwell, as unlicensed “stem cell clinics” may pose safety and ethical risks. Moreover, emerging research on MSC-derived exosomes offers exciting potential to overcome many current limitations by delivering therapeutic molecules without the complexities of live-cell transplantation [2].
The Future: Regenerative therapy at Stemwell and DNA GTx
The next generation of therapies will likely combine MSC technology, induced pluripotent stem cells (iPSCs), and biologic agents to enhance both precision and durability of immune repair. At Stemwell, we specialize in cell therapy, developing advanced MSC-based and exosome approaches to promote tissue repair and immune modulation. At DNA GTx, we focus on genomics, using genome-guided strategies to optimize immune responses and support personalized regenerative therapies. These combined innovations represent a paradigm shift from conventional disease suppression toward immune retraining and tissue restoration, a transformative goal long sought by patients, clinicians, and researchers alike.
Rheumatic Disease Day: A Call to Awareness
On Rheumatic Disease Day, we celebrate both scientific progress and the resilience of patients living with autoimmune diseases. Stem cell therapy embodies a message of hope, but also of responsibility. While early data are encouraging, these therapies remain under investigation, and participation in controlled clinical trials ensures both safety and scientific advancement.
By continuing to invest in ethical research, patient-centered trials, and global collaboration, we move closer to a future where autoimmune rheumatic diseases are not only managed, but potentially healed from within.
References
- Dudek D., Walczuk E, Wajda A, Paradowska-Gorycka A. Mesenchymal stem cells in systemic sclerosis therapy. Reumatologia. 2020 Oct 18;58(5):324–330. doi: 10.5114/reum.2020.99995
- Yang G., Fan X, Liu Y, et al. Immunomodulatory Mechanisms and Therapeutic Potential of Mesenchymal Stem Cells. Stem Cell Rev Rep. 2023 Apr 14;19(5):1214–1231. doi: 10.1007/s12015-023-10539-9
- Zeng L, Zhang Y, Li 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 Research & Therapy. 2025;16(1):65. doi: 10.1186/s13287-025-04184-x
-
Mesa LE, Zhang Y, Li Y, et al. Safety and efficacy of mesenchymal stem cells therapy in rheumatoid arthritis: a systematic review and meta-analysis of clinical trials. PLoS One. 2023 Jul 27;18(7):e0284828. doi: 10.1371/journal.pone.0284828.
-
Jin L, Ding M, Cui S, et al. Human Umbilical Cord Mesenchymal Stem Cells Modulate Cytokine Secretion of CD4+ T Cell in Systemic Lupus Erythematosus by Inhibiting HSP90AA1 in the Glucose‐Activated PI3K‐AKT Pathway. Immun Inflamm Dis. 2025 Aug 13;13(8):e70239. doi: 10.1002/iid3.70239
- El-Jawhari JJ. Et al. Mesenchymal stem cells, autoimmunity and rheumatoid arthritis. QJM: An International Journal of Medicine, Volume 107, Issue 7, July 2014, Pages 505–514, https://doi.org/10.1093/qjmed/hcu033
- Alberto M Marmont du Haut Champ et al. Hematopoietic Stem Cell Transplantation for Systemic Lupus Erythematosus. Clin Dev Immunol. 2012 Aug 30;2012:380391. doi: 10.1155/2012/380391
Ready to learn more about stem cell therapy?
At Stemwell, our team of doctors are highly skilled in successfully supporting thousands of people with a range of stem cell treatments. If you would like to learn more about stem cell therapy you can contact us with any questions, or apply today to check your eligibility.
