This article looks at promising early-stage research on stem cell therapy for rheumatoid arthritis

There hasn’t been tons of research done on this area, but we’ve broken down all the latest studies & reviews for you here. We know there’s a lot to go through! Each study has a short summary and our conclusion at the end of this article sums it all up.

We hope this helps shed some light on Stem Cells treating RA!

Phase 1 Trials looking at Stem Cell Research for RA

Allogenic Bone Marrow-Derived Clonal MSC Therapy for Refractory Rheumatoid Arthritis: Phase 1: Iran 2024

You can read more about the study here (PubMed link).

This clinical study tested whether monthly IV infusions of bone marrow-derived clonal mesenchymal stromal cells (BM-cMSCs), taken from healthy donors could help people with severe rheumatoid arthritis (RA) who had not improved with traditional medications.

Unlike many stem cell studies that use fat-derived or unselected stem cells, this one used a purified, clonal population of bone marrow MSCs, which may have more consistent immune-calming effects.  A clonal population means all the stem cells come from one original cell, so they’re all the same and work in a consistent way.

The goal was to see if this cell type could reduce joint pain, improve physical function, and shift inflammatory markers in the blood.

This was a Phase I safety trial, meaning it focused primarily on whether the treatment caused side effects. Researchers also looked at early signs of benefit. It was conducted in Iran by a team of clinical and stem cell scientists at institutions including the Royan Institute.

Study Details

• Participants
  • 6 adults with refractory RA, meaning they had not responded to standard drugs like DMARDs
  • All had active joint inflammation at the start of the study
• Procedure
  • Each patient received 3 intravenous infusions, given once a month over 24 weeks
  • The stem cells came from healthy donors’ bone marrow, not from the patients themselves
  • Cells were clonally selected and expanded in a lab to ensure consistency
• Dosage
  • Exact number of cells per infusion was not reported in the abstract
    

Key results

• Joint Pain & Function
  • VAS (pain scale) improved in half the patients
  • ACR20 means a patient had at least a 20% improvement in joint pain, swelling, and physical function. In this study, 4 out of 6 patients met that goal, which is a standard sign that a rheumatoid arthritis treatment is working.
  • Doctors use scores called SDAI and CDAI to measure how active someone’s rheumatoid arthritis is, including joint pain, swelling, and overall health. In this study, 3 out of 6 patients showed lower scores, meaning their disease became less active and symptoms improved.
• Inflammatory Blood Markers

These trends suggest the stem cells may have reduced harmful inflammation without wiping out the immune system.

Safety

• No serious side effects reported
• IV infusions were well tolerated
• No reports of allergic reactions, infection, or organ issues

What We Don’t Know

• The exact dosage hasn’t been shared publicly yet
• The study was very small (6 patients) with no placebo group
• Long-term effects beyond 24 weeks are unknown
• Imaging (MRI, ultrasound) and joint repair markers were not part of the study

Conclusion

This small, early-stage clinical trial suggests that:

• Clonal bone marrow-derived MSCs may be safe when given by IV to people with severe, drug-resistant RA
  
• Patients showed real improvements in joint pain and inflammation
  
• No serious safety issues occurred over the 24-week study

While more research is needed, this trial provides early evidence that lab-expanded MSCs from healthy donors could offer a future therapy option for difficult-to-treat autoimmune diseases like RA.

Hope BioSciences Autologous Adipose-Derived MSC Therapy for Active Rheumatoid Arthritis: USA 2022

You can read more about the study here.

This clinical study tested whether a single intravenous (IV) dose of mesenchymal stem cells (MSCs), taken from each patient’s own fat tissue (adipose), could reduce symptoms in people with active rheumatoid arthritis (RA), even if they were already on standard medications like DMARDs.

The goal was to evaluate whether these autologous adipose-derived MSCs could safely reduce joint pain and swelling and possibly improve systemic inflammation. Unlike some immune-reset studies, this one focused more on joint function outcomes than immune cell profiles.

This was a Phase I/IIa, open-label, non-randomized pilot study, meaning it was designed to check for safety and early signs of benefit. Not to compare against a placebo group. It was led by researchers at Hope Biosciences Stem Cell Research Foundation in Texas, USA.

Study Details

• Participants
  • 15 adults with active rheumatoid arthritis
  • All had at least 6 swollen and 6 tender joints
  • Most were already taking DMARDs or glucocorticoids, but still had symptoms
  • 13 patients completed the full 52-week follow-up
  • Average age: 52 years old
  • Mostly female (93%)
  • Average disease duration: ~11.4 years
  • Recruited from two clinics in Houston, Texas

Procedure

• Delivery Method: Each patient received a single IV infusion of stem cells
• Cell Type & Source:
  • Autologous mesenchymal stem cells (MSCs)
  • Source: Each patient’s own fat tissue (3–5 mL)
  • Cells were isolated and culture-expanded in a lab using Hope Biosciences’ proprietary protocols
• Dosage: Fixed dose of 200 million live MSCs (2 × 10⁸ cells)

Key Results

• Joint Function (ACR 66/68 Scores)
  Doctors used a joint scoring system that looks at 66 swollen and 68 tender joints, including the feet (more comprehensive than usual scoring methods):
  

Most patients saw a dramatic drop in joint inflammation, from double-digit joint swelling and pain down to nearly none, after just one infusion.

That’s a clinically significant improvement and it lasted for a full year.

• Inflammatory Blood Markers
  • Blood tests for immune system activity showed mixed results:

• This suggests the stem cells helped local joint inflammation, but did not cause a clear shift in systemic immune balance in this single-dose study.
  

Safety

• No serious adverse events
• Only 4 side effects were possibly linked to treatment (e.g., mild anemia or itching)
• No infusion reactions, liver or kidney issues
• One minor lab change: albumin-to-globulin ratio shifted slightly, but was not clinically important
• Overall, the treatment was well-tolerated and safe across the full 52-week follow-up.

How the Cells Worked

The researchers believe the stem cells helped by reducing inflammation in the joints, not by turning into cartilage or bone.

They propose:

• MSCs may have released anti-inflammatory molecules into the bloodstream or joint tissue
  
• The improvements likely came from immune modulation, not tissue regeneration
  
• Because the cells were fresh and viable (>94% alive), their function may have been stronger than typical frozen stem cells, which may lose potency when thawed
  
• However, the study did not measure Treg cells, IFN-γ, or other markers of immune “reset”, so systemic rebalancing can’t be confirmed.
  

What We Don’t Know

• There was no placebo group, so placebo effect or natural fluctuations can’t be ruled out
• The study was small (15 patients), so larger trials are needed
• It didn’t measure MRI imaging, joint repair, or cartilage regeneration
• Systemic immune activity (e.g. Treg increases, cytokine balance) was not fully assessed
• Only one single infusion was tested, multiple doses may have broader effects

Conclusion

This study shows that a single IV dose of fresh, autologous adipose-derived MSCs may be safe and highly effective at reducing joint inflammation and symptoms in patients with active rheumatoid arthritis.

• Joint swelling and pain improved dramatically
• No major side effects were observed
• Systemic immune changes were minimal, but local benefit was clear

While more research is needed to confirm these results in larger, placebo-controlled trials, this study provides strong early evidence that stem cell therapy can safely reduce symptoms in difficult-to-treat RA, especially when cells are freshly prepared from a patient’s own fat tissue.

Autologous Bone Marrow MSC Therapy for Refractory Rheumatoid Arthritis: Iran 2019

You can read more about the study here.

This clinical study tested whether a single intravenous (IV) dose of autologous mesenchymal stem cells (MSCs), taken from each patient’s own bone marrow, could help rebalance the immune system and reduce symptoms in people with refractory rheumatoid arthritis (RA) (RA that doesn’t respond to standard treatments).

The goal was to evaluate whether stem cell therapy could increase the body’s own immune regulators (like Tregs) and reduce harmful inflammation. The team focused on measuring how the body’s immune cells changed after treatment, not just whether symptoms improved.

This was a single-arm, investigator-led study, meaning it focused on safety and early biological effects, not direct comparison against a placebo group. The work was led by clinical immunologists and rheumatologists at Mashhad University of Medical Sciences.

Study Details

Participants:

• 13 adult women with refractory rheumatoid arthritis
  
• All had been on maximum doses of standard treatments (DMARDs) with poor results
  
• Recruited from Imam Reza Hospital in Mashhad, Iran
  
• Average age: 44 years old
  
• Average disease duration: 12 years
  
• Patients were followed up at 1 month, 6 months, and 12 months after infusion

Delivery Method

• Each patient received a single IV infusion of stem cells
  
• No surgery required, cells were delivered through a standard IV drip
  
• Cells were prepared in accordance with a prior protocol published by the same research team

Cell Type & Source

• Autologous mesenchymal stem cells (MSCs)
  
• Source: Patient’s own bone marrow
  
• Cells were expanded in the lab prior to infusion

Dosage

• 1 million cells per kilogram of body weight (1 × 10⁶/kg)
  
• Single dose per patient

Key Results

• Safety
  • No serious adverse events were reported during the 12-month study
  • No infections, allergic reactions, or immune-related complications
• Immune System Changes
  from PBMC analysis:a lab test where a patient’s immune cells are isolated from their blood and studied to see how they react after treatment
  • FOXP3 is a gene that tells the body to make more regulatory T cells, the immune cells that calm down inflammation. At 12 months after treatment, this gene was much more active, meaning the body was likely making more of these calming cells to help control the autoimmune attack.
  • IL-10 is an anti-inflammatory signal produced by the immune system to help reduce damage. After treatment, IL-10 levels more than doubled. Going from about 825 to 1,898 pg/ml, showing that the body was creating more of these calming signals to help control inflammation.
    
  • TGF-β is another anti-inflammatory molecule that helps the immune system stay balanced. After treatment, its levels went up from about 1,063 to 1,699 pg/ml, suggesting the body was creating more signals to support healing and reduce autoimmune activity.
    
  • TNF-α is a major cause of inflammation and joint damage in rheumatoid arthritis. After treatment, its levels dropped significantly by 6 months, showing that the immune system was becoming less aggressive.
  • IL-4 is a signal that can promote certain immune responses linked to autoimmunity. After treatment, IL-4 levels went down, suggesting the immune system was becoming more balanced and less likely to trigger harmful Th2 activity.
    
  • IL-17A and IFN-γ are inflammatory signals made by active immune cells. After treatment, their levels didn’t change much, meaning the therapy mainly affected other parts of the immune system, especially those linked to regulation, not attack.
• Clinical Improvements
  • DAS28-ESR scores, which track RA severity, improved across the board. DAS28-ESR is a standard score doctors use to measure how active rheumatoid arthritis (RA) is. It looks at things like joint swelling, pain, and blood inflammation markers. A higher score means more severe disease, and a lower score means improvement:
    • From 5.56 (severe) before treatment to 4.72 at 12 months
    • Statistically significant reductions seen at 1, 6, and 12 months

How the Cells Worked

• The researchers believe the MSCs helped by rebalancing the immune system, not by replacing tissue. Here’s what they propose:
  • MSCs released healing molecules that shifted the immune system away from inflammation
    
  • Increased regulatory T cells (Tregs), the “brakes” of the immune system which helped reduce autoimmune attacks
    
  • Reduced inflammatory cytokines like TNF-α, which play a major role in RA joint damage
    
  • Improved balance of helper T cell subsets, making the immune response more stable
• They did not observe any transformation of the MSCs into other tissue types. The benefit came from the immunoregulatory signals the cells released.
  

What We Don’t Know

• The study had no placebo group, so natural variation or placebo effects can’t be ruled out
• Sample size was very small (13 patients)
• The MSC culture protocol was not fully reprinted, though referenced
• Longer-term effects (beyond 12 months) are unknown
• No data on MRI, joint imaging, or long-term joint function were included

Conclusion

This small but promising study shows that a single IV dose of autologous bone marrow MSCs may be safe and immunologically effective in patients with treatment-resistant rheumatoid arthritis.

• Patients showed a clear shift toward immune balance, especially increased Treg activity and anti-inflammatory cytokines
  
• Clinical scores improved, and no serious side effects were reported
  
• While more research is needed, this study supports the idea that stem cell therapy could calm the immune system, not by suppressing it, but by helping it regulate itself
  

Reviews looking at Stem Cell Research for RA

A review is a type of scientific paper where researchers summarize and analyze the results of many past studies on a topic, instead of running their own new experiment.

It’s like reading all the available evidence and then explaining what it shows overall. What’s working, what isn’t, and where the gaps are.

Unlike a clinical trial, which tests a treatment on real patients, a review pulls together findings from multiple trials to give a big-picture view.

2025 Review on Mesenchymal Stem Cell Transplantation for Autoimmune & Rheumatic Diseases: China

You can read the full review here.

A team of researchers in China from institutions including Nanjing Drum Tower Hospital and Peking Union Medical College Hospital reviewed all available randomized controlled trials using mesenchymal stem cell  transplantation to treat a range of autoimmune and rheumatic diseases.

Unlike other types of stem cell therapy that aim to completely wipe out and replace the immune system, MSCs work differently. They are multipotent “medicinal” cells that modulate the faulty immune system, reduce inflammation, and can help repair damaged tissue by differentiating into new cells.

The researchers focused on MSCs because these cells offer a unique, two-pronged approach of calming the immune system and promoting regeneration, making them a promising alternative for severe cases where traditional drugs have failed.

What They Looked At

The researchers analyzed 42 randomized controlled trials (RCTs) involving a total of 2,183 patients. They focused exclusively on RCTs to ensure a high standard of evidence.

The review covered eight different autoimmune and rheumatic diseases:

• Rheumatoid Arthritis (RA)
• Osteoarthritis (OA)
• Spondyloarthritis
• Systemic Sclerosis (SSc)
• Systemic Lupus Erythematosus (SLE)
• Inflammatory Bowel Disease (IBD)
• Multiple Sclerosis (MS)
• Primary Sjögren’s Syndrome (PSS)

What They Wanted to Find Out

• Does MSC transplantation improve symptoms and disease activity in patients with these conditions?
• Is the treatment safe? What are the risks?
• Is there a difference in effectiveness based on where the MSCs come from (e.g., bone marrow, adipose tissue, umbilical cord)?
• What is the optimal cell dosage, and is early intervention better?

What They Found

1. Effectiveness (Symptom Improvement)
   • Strongly Effective For: MSCs significantly improved symptoms in OA (pain reduction), SLE (reduced disease activity and improved kidney markers), and IBD (improved clinical efficacy).
   • Also Effective For: The review indicates MSCs also improve symptoms in RA, Spondyloarthritis and PSS.
   • Not Effective For: The meta-analysis showed that MSCs did not significantly improve symptoms for MS or SSc when compared to control groups.
2. Mechanism of Action
   • The review explains that MSCs don’t just act like a drug; they work by actively changing the body’s environment.
   • Immunomodulation: They calm the immune system by inhibiting inflammatory T and B cells, reducing harmful cytokines (like TNF-a), and promoting the growth of “good” regulatory T-cells (Tregs).
   • Tissue Regeneration: They can travel to sites of damage and differentiate into new tissue cells, such as cartilage in joints affected by arthritis.
   • Specific Mechanism for PSS: The authors highlight a novel mechanism from their own research, where MSCs work by encouraging dendritic cells to secrete a specific anti-inflammatory molecule called IL-27.
3.  Stem Cell Sources
   • The studies used MSCs derived from three main sources: bone marrow, umbilical cord, and adipose (fat) tissue.
   • For Osteoarthritis, cells from all three sources were effective at reducing pain. Adipose-derived MSCs showed the most comprehensive benefit, also improving physical function and overall WOMAC scores.
4. Dosage and Delivery
   • Dosage: Based on their analysis and experience, the authors recommend an optimal dose of around 1 million cells per kg of body weight. They also suggest that multiple doses may be more effective than a single one.
   • Delivery Method: Cells were delivered either through local intra-articular injections (for knee OA) or systemic intravenous (IV) infusion for other diseases.
5. Safety
   • Overall, MSC transplantation was found to be safe.
   • The meta-analysis showed that MSCs did not increase the incidence of adverse events compared to placebo or conventional therapy. This held true for OA, SLE, IBD, and MS.
6. Limitations in the Studies Reviewed
   • A key issue is that the efficacy of MSCs was inconsistent across studies, which the authors attribute to variations in the cell sources, cultivation methods and treatment protocols used in different trials.
   • For some diseases like RA, SSc, and Spondyloarthritis, there are not enough high-quality RCTs to draw definitive conclusions
     

What They Concluded

MSC transplantation has the potential to be a safe and effective treatment for several autoimmune and rheumatic diseases, especially for patients who have not responded to other therapies.

The treatment is not a “one-size-fits-all” solution. The authors make several key recommendations for its use:

• Use it early: MSC therapy is preferable in earlier stages of a disease, as efficacy decreases in advanced stages.
• Combine therapies: It should be combined with other treatments for maximum benefit rather than being used alone.
• Standardize protocols: Before MSCs can become a standard treatment, there is a critical need for larger, multi-center clinical trials with standardized protocols to confirm the best cell sources, doses, and timing for each disease

2021 Review on Hematopoietic Stem Cell Transplantation (HSCT) for Rheumatoid Arthritis: India

You can read the full review here.

A team of researchers in India from institutions including Sharda University, Sri Lalithambigai Medical College and Government Medical College Dindigul reviewed all the available human studies using hematopoietic stem cell transplantation (HSCT) to treat rheumatoid arthritis (RA).

HSCT works in two steps: First, doctors give high-dose immunosuppressive drugs to wipe out the faulty immune system causing the disease. Then, hematopoietic stem cells are infused to rebuild a new, healthier immune system from scratch.

The researchers focused on HSCT because rheumatoid arthritis is an autoimmune disease. HSCT offers a way to “reset” the immune system by removing harmful immune cells and rebuilding tolerance. They saw this as potentially more effective for severe, drug-resistant cases than conventional or biologic therapies

What They Looked At

The researchers analyzed 17 clinical studies involving 233 patients with rheumatoid arthritis who received HSCT.

These included:

• 1 randomized controlled trial (RCT)
  
• 11 prospective studies
  
• 5 retrospective case reports or series

All patients had severe RA that didn’t respond to standard drugs like DMARDs or newer biologic therapies.

What They Wanted to Find Out

• Does HSCT help improve symptoms in patients with severe, drug-resistant RA?
  
• How long does remission last after HSCT?
  
• What are the side effects or risks?
  
• Is there a difference between autologous (your own cells) and allogeneic (donor cells) transplants?
  
• What’s the best combination of drugs to prepare the body for HSCT?
  
• Should certain immune cells be removed from the graft?
  
• When is the best time in the disease to do HSCT?
  

What They Found

1. Effectiveness (Short-Term Improvement)
   • Significant improvement in symptoms up to 24 months after HSCT
   • After 2 years, the benefit was no longer statistically significant
   • Both autologous and allogeneic HSCT showed short-term success
   • HSCT improved scores on the ACR 50/70 criteria, which measure how much better patients felt
2. Mechanism of Action
   • HSCT doesn’t repair joints or act like a painkiller. It works by:
     • Wiping out autoimmune cells using powerful drugs
     • Allowing new immune cells to grow from the transplanted stem cells
     • Possibly triggering a “graft-versus-autoimmune” effect in donor (allogeneic) transplants, where donor cells fight off remaining harmful ones
   • The goal is immune tolerance, getting the body to stop attacking its own joints.
3. Stem Cell Sources and Preparation
   • 14 out of 17 studies used autologous HSCT (your own cells)
   • 3 used allogeneic HSCT (donor cells)
   • Most studies selected CD34+ stem cells, which are known to form blood and immune cells
   • Some studies depleted T cells to prevent bringing autoimmune cells back
4. Mobilization & Conditioning Drugs (Dosages)
   • To collect and prepare for HSCT, they used:
     • Cyclophosphamide (CYC): 1.5–4 g/m² for mobilization; 100–200 mg/kg for conditioning
       This chemotherapy drug helps both to release stem cells into the blood for collection and to wipe out the faulty immune system before the transplant.
     • G-CSF (growth factor): 5–10 µg/kg
       This is a natural protein that encourages the bone marrow to push stem cells into the bloodstream where they can be collected.
     • ATG, Busulfan, Fludarabine, Alemtuzumab: in some protocols, especially in donor transplants
       These are powerful immune-suppressing drugs used in certain cases to prevent immune rejection or graft-versus-host disease, especially when the stem cells come from a donor
   • These drugs suppress the immune system and help collect the right cells.
5. Delivery Method
   • Cells were returned to the patient through infusion (like a blood transfusion)
   • No complex surgeries were involved
6.  Safety
   • Overall, HSCT was relatively safe:
     • Only 2 deaths out of 233 patients (<1%)
     • No major drug toxicities reported
   • Infection was the biggest concern, especially in donor HSCT cases where stronger immunosuppression was needed
   • Infection was the biggest concern, especially in donor HSCT cases where stronger immunosuppression was needed
7.  Limitations in the Studies Reviewed
   • Small sample sizes in many studies (<15 patients)
   • Only one RCT,  most were single-arm studies without a comparison group
   • Varied drug protocols, follow-up times, and outcome measures
   • No long-term data beyond 5 years
     
     

What They Concluded

• HSCT can offer temporary relief and immune rebalancing for people with severe, treatment-resistant RA, but it is not a permanent cure.
• The treatment worked best for up to 2 years, especially in patients with early, aggressive disease and good physical condition.
• Before HSCT becomes a standard option for RA, we need:
  • Larger, standardized, multi-center clinical trials
  • Longer follow-up (5+ years)
    
    
    

Summary of Stem Cell Research for RA

Stem cell therapy for rheumatoid arthritis (RA) is still in its early stages, but early trials suggest it could be a safe and promising option for people who haven’t responded to standard treatments. Here’s what the research shows so far:

Most Studied Cell Types
The main cell type being tested is the mesenchymal stem cell, usually taken from bone marrow, fat tissue, or donated umbilical cords. Some studies use a patient’s own cells (autologous), while others use donor cells (allogeneic) that have been lab-grown for consistency.

Success Rates
In small trials, between 50% to 75% of patients saw noticeable improvements in joint pain, swelling, and function, often after just one to three infusions. For example, in a Phase I study in Iran, 4 out of 6 patients reported meaningful relief. However, since these studies are small and don’t include placebo groups, more data is needed to confirm the results.

No Proof of Joint Regeneration (Yet)
The improvements were in how people felt, less pain, more mobility. Not in physically repairing joints or cartilage. No human study in this article confirmed regeneration on MRI or imaging scans.

How the Cells Work
MSCs don’t become new joint tissue; instead, they release healing molecules that calm the immune system and reduce inflammation. This can lead to less pain and better movement, especially in cases where the immune system is attacking the joints.

HSCT cells work differently. Instead of regulating the immune system like MSCs do, HSCT aims to completely reset it by first wiping it out with strong chemotherapy or immunosuppressive drugs, then rebuilding it from scratch using blood-forming stem cells. It’s a much more aggressive approach, often used in severe cases, and comes with higher risks, but may offer deeper immune reprogramming in some patients.

Who’s Leading the Research?
Much of the research is happening in Iran, China and the US. Independent foundations and government-backed hospitals are driving early-phase trials, with growing interest worldwide.

Is One Type of Stem Cell Better?
There’s no clear winner yet. Some studies suggest that freshly prepared, fat-derived MSCs may have strong local anti-inflammatory effects, while donor-derived bone marrow cells show immune-modulating potential. But each method is still being tested in small groups.

Best Way to Deliver the Cells?
All studies used intravenous (IV) infusion. aA simple, non-invasive method that was safe and well tolerated. There were no serious side effects reported in any of the trials reviewed.