SCIENTIFIC STUDY REVIEW
Featured Article: Mesenchymal stem cells for immune modulation in systemic lupus erythematosus: From bench research to clinical applications
Original article: https://pmc.ncbi.nlm.nih.gov/articles/PMC11731813/
Systemic lupus erythematosus, or SLE, is a chronic autoimmune disease in which the immune system attacks the body’s own tissues. The disease can affect the kidneys, joints, skin, blood cells, nervous system, and other organs. Standard treatment often relies on steroids and other medications that suppress immune activity, but these treatments do not work equally well for everyone and can produce significant adverse effects when used long term.
This has led researchers to study mesenchymal stem cells, also called mesenchymal stromal cells or MSCs, as a possible way to regulate abnormal immune activity.
This review by Ginting and colleagues examined how MSCs interact with the immune system in SLE and summarized laboratory, animal, and clinical research involving MSC therapy.
Purpose and Methodology
The authors reviewed research on the immune abnormalities involved in lupus, the immunomodulatory properties of MSCs, laboratory studies examining how MSCs interact with immune cells, and published clinical studies involving patients with SLE.
The review also examined several factors that may affect treatment response, including MSC source, dose, patient characteristics, background immunosuppressive therapy, and the inflammatory environment surrounding the cells.
This publication is a narrative review rather than a clinical trial, systematic review, or meta-analysis. The authors summarize evidence from different types of studies to explain biological mechanisms and assess the current state of MSC research in lupus.
How MSCs May Affect the Lupus Immune Response
SLE involves abnormalities in both the innate and adaptive immune systems. B cells may produce antibodies against the body’s own tissues, dendritic cells can become excessively activated, and the balance between different types of T cells may become disrupted.
MSCs appear capable of interacting with several of these immune pathways.
The review describes evidence that MSCs may reduce the activation and proliferation of certain T cells and B cells, influence dendritic cells, and increase regulatory immune cells that normally help prevent excessive immune responses.
Of particular interest are regulatory T cells, or Tregs, which help maintain immune tolerance. Tregs are often reduced or functionally impaired in patients with SLE. Experimental studies suggest MSCs may increase Treg activity and release substances such as IL-10, TGF-β, IDO, and prostaglandin E2 that contribute to immune suppression.
The review also discusses regulatory B cells, or Bregs. These cells can release anti-inflammatory signals and help limit abnormal immune activity. MSC administration has been associated with increased Breg populations in experimental models, providing another possible mechanism for restoring immune balance.
MSCs may also inhibit B-cell proliferation and differentiation into antibody-producing cells, which is relevant because abnormal antibody production is a central feature of lupus.
The Immune Environment Matters
One of the more important findings in the review is that MSCs do not behave the same way under all conditions.
Their activity depends partly on the inflammatory environment surrounding them.
High concentrations of inflammatory signals such as interferon-gamma, TNF-alpha, and IL-1 beta may “license” MSCs to become more immunosuppressive. Under other conditions, however, MSCs may show less suppressive or even pro-inflammatory activity.
The authors describe this as an important source of uncertainty because the immune environment can vary considerably between patients and at different stages of lupus.
Toll-like receptors, or TLRs, may also influence how MSCs respond. Different MSC sources can express different TLR patterns, and stimulation of these receptors may alter whether MSCs promote or suppress inflammation.
This means MSC therapy is not simply a matter of administering cells. The condition of the cells, their source, and the patient’s immune environment may all affect the outcome.
What the Clinical Evidence Showed
Most clinical research summarized in the review involved patients with severe or treatment-resistant SLE, often including lupus nephritis.
Several early studies reported encouraging findings.
A 2010 pilot study involving 15 patients with refractory SLE reported improvements in kidney function, antibody levels, fatigue, and other measures following bone-marrow MSC treatment. An increase in Tregs was also observed.
A larger prospective study followed 87 patients with severe or refractory SLE for four years. Complete remission was reported in 28% of patients after one year and 31% after two years, although approximately 23% experienced relapse. Improvements in disease activity scores and proteinuria were also reported.
Other uncontrolled studies involving bone-marrow or umbilical-cord MSCs similarly reported reductions in disease activity, proteinuria, or immunosuppressive medication use.
However, these studies generally lacked placebo groups, making it difficult to determine how much of the improvement was caused by MSC treatment rather than standard therapy, disease fluctuation, or patient selection.
A particularly important study was a 2017 randomized, double-blind, placebo-controlled trial involving patients with lupus nephritis. Proteinuria decreased in both groups. However, the investigators found no significant differences between MSC and placebo recipients in renal function, lupus activity scores, or overall patient outcomes.
This controlled finding is important because it provides a more cautious picture than many of the earlier uncontrolled studies.
A 2022 Phase I study involving six patients with active SLE found that five met the study’s primary response criteria by 24 weeks and showed improvements in several laboratory markers. However, the very small sample size limits conclusions about effectiveness.
Safety and Treatment Variability
MSC administration was generally described as feasible and reasonably well tolerated, but adverse events were reported.
Across the clinical studies summarized in the review, these included infections, pneumonia, herpesvirus infections, diarrhea, nausea, flushing, headache, and other reactions. Some studies also reported deaths, although these were not always attributed directly to MSC treatment.
A long-term safety analysis involving patients with several autoimmune diseases found mild to moderate acute reactions in approximately 12% of patients, including fever, headache, palpitations, flushing, insomnia, and gastrointestinal symptoms.
The studies also differed considerably in MSC source and dosing. Bone-marrow, umbilical-cord, and adipose-derived MSCs were all used, and treatment protocols varied substantially.
These differences make it difficult to determine whether one type of MSC, dose, or treatment schedule is more effective than another.
Key Limitations of the Evidence
The clinical evidence remains limited by several recurring problems.
Most studies involved small numbers of patients with severe or refractory disease. Many lacked control groups or randomization, and patients often continued receiving steroids or other immunosuppressive medications.
Baseline disease severity, previous treatments, MSC source, dose, treatment frequency, and outcome measures also differed across studies.
The authors specifically note that MSC therapy has not been adequately studied in newly diagnosed SLE. They call for larger studies with more consistent enrollment criteria, standardized clinical outcomes, better-defined dosing, and clearer approaches to background immunosuppressive therapy.
What the Review Means for Patients
The review provides a credible biological explanation for why MSCs might influence lupus.
The cells interact with T cells, B cells, dendritic cells, Tregs, Bregs, and inflammatory signaling pathways that are directly involved in SLE.
However, evidence that MSCs can alter these immune mechanisms does not by itself establish that treatment produces meaningful or lasting clinical benefit.
The strongest clinical evidence remains mixed, and the favorable results from uncontrolled studies need to be confirmed in larger randomized trials.
Clinical Takeaway
In this review, Ginting and colleagues show why MSCs remain an important area of lupus research. Their ability to regulate multiple parts of the immune system may offer a different approach from traditional broad immunosuppression.
At the same time, MSCs are not a uniform treatment. Their behavior can be affected by tissue source, dose, manufacturing, patient characteristics, and the inflammatory environment in which they are administered.
Early studies in refractory SLE and lupus nephritis have reported encouraging improvements, but much of the evidence comes from small or uncontrolled studies. The randomized placebo-controlled findings have been less definitive.
The evidence supports further clinical research rather than broad claims of effectiveness. Larger randomized trials, standardized MSC products, clearer dosing protocols, consistent outcome measures, and longer follow-up are needed before the role of MSC therapy in SLE can be established.
Patients should not discontinue prescribed lupus medications or replace care from a qualified physician based on these findings.
Reference
Ginting AR, Munir D, Amin MM, et al. Mesenchymal stem cells for immune modulation in systemic lupus erythematosus: From bench research to clinical applications. Narra J. 2024;4(3):e994. doi:10.52225/narra.v4i3.994.
Regulatory Disclaimer
This review is provided for educational and informational purposes only and comments on published literature involving experimental cell-based approaches. The findings do not establish a treatment as safe or effective for any individual and should not be interpreted as medical advice. Patients should consult a qualified physician before changing prescribed care.