image: Characteristics of MSCs and their and therapeutic mechanisms in rheumatoid arthritis. MSC, mesenchymal stromal cell; Tfh, T-follicular helper; Th, T helper; Treg, regulatory T cells.
Credit: Rheumatology & Autoimmunity
Rheumatoid arthritis (RA), a chronic autoimmune disease affecting 0.5% to 1% of the global population, causes erosive joint damage, pain, and systemic complications, often leading to disability. Conventional treatments (nonsteroidal anti-inflammatory drugs, NSAIDs; disease-modifying antirheumatic drugs, DMARDs; biologics) ease symptoms temporarily but carry severe side effects (gastrointestinal harm, infections) and fail to address root causes.
In a new review in the journal Rheumatology & Autoimmunity, researchers led by Dr. Yingjia Chen (Lotus Lake Capital) position mesenchymal stromal cell (MSC) therapy as a transformative RA solution, synthesizing preclinical and clinical evidence of its long-term efficacy and safety.
Why Conventional RA Treatments Fall Short
RA stems from dysregulated immune responses attacking joints. Traditional options have critical flaws:
- NSAIDs/glucocorticoids: No joint protection; long-term use risks osteoporosis, bleeding.
- DMARDs: Liver/kidney toxicity.
- Biologics: Costly, raise infection/malignancy risks, and lose efficacy over time.
MSCs: Unique Therapeutic Advantages
Found in umbilical cord, bone marrow, and adipose tissue, MSCs target RA via four key traits:
1. Immunomodulation: Suppress overactive immune cells, cut pro-inflammatory cytokines (TNF-α, IL-6), and restore balance.
2. Tissue repair: Differentiate into cartilage/bone cells, secrete growth factors (IGF-1, VEGF) to heal damage.
3. Low immunogenicity: Safe donor-derived use with minimal rejection risk.
4. Targeted migration: Home in on inflamed joints via chemokine receptors.
Multiple clinical studies (1-3-year follow-ups included) confirm sustained benefits of MSC therapy for RA patients. For instance, a 3-year study of 64 refractory RA patients by Yongjun Liu team showed MSCs + low-dose DMARDs sustainedly reduced inflammatory markers (ESR, CRP) and improved DAS28/HAQ scores, with no serious adverse events. Additionally, MSC therapy has low infection/allergy rates, no elevated long-term tumor risk, and better safety than traditional immunosuppression.
Path to Broad Use
The review outlines strategies to optimize MSCs, such as:
- Personalized selection: UC-MSCs for accessibility, bone marrow MSCs for severe damage.
- Combinations: MSCs + low-dose DMARDs enhance outcomes.
Journal
Rheumatology & Autoimmunity
Method of Research
Literature review
Subject of Research
Not applicable
Article Title
Mesenchymal stromal cell therapy for rheumatoid arthritis: Long-term efficacy, safety, and mechanistic insights
Article Publication Date
18-Dec-2025
COI Statement
Lingyun Sun is a member of the Rheumatology & Autoimmunity editorial board and is not involved in the peer-review process of this article. The remaining authors declare no conflict of interest.