Does stem cell safety hold up years after treatment? A Korean study followed nine patients with rheumatoid arthritis for five years after a single infusion of cord blood-derived cells. Its main finding concerns long-term safety, the hardest information to obtain in this field.
Why long-term stem cell safety data matter
Early-phase clinical trials usually follow patients for a limited period. That is enough to see the immediate effects of a treatment, but not the late ones. In fact, some risks, such as infections, cardiovascular events or tumours, can appear years later.
This is why a five-year follow-up carries particular weight. It shows whether stem cell safety holds over time, not just in the first weeks.
Rheumatoid arthritis: what current drugs leave open
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease. It mainly targets the synovial membrane, the thin tissue that lines the joints. Without good control, the inflammation slowly destroys the joints and can cause serious disability.
Over the past two decades, biologic (bDMARDs) and targeted synthetic (tsDMARDs) antirheumatic drugs have radically changed the outlook. However, long-term use of these drugs, which act on the immune system, carries some risks. For example, it raises the risk of infections such as tuberculosis, hepatitis B and herpes zoster. It also brings cardiovascular risk and, according to some analyses, a possible rise in cancer risk.
This gap is where interest in cell therapies comes from. Scientists are also studying them in other autoimmune diseases, as we described in our article on a real-world study in 120 patients.
How cord blood stem cells act on the immune system
Mesenchymal stem cells (MSCs) are multipotent, non-haematopoietic cells, which means they do not give rise to blood cells. They can renew themselves and help repair tissue. Their most interesting property, however, is another one: they modulate the immune response.
MSCs work on several levels. First, they slow the maturation of dendritic cells and the activation of natural killer cells. Next, they curb the excessive growth of T and B lymphocytes. Finally, they promote the production of regulatory T cells (Tregs), which help restore immune tolerance.
Preclinical studies, in laboratory and animal models, describe further effects. For example, MSCs shift macrophages from the M1 (pro-inflammatory) to the M2 (anti-inflammatory) state. They also lower TNF-α and IL-17, raise IL-10 and inhibit osteoclastogenesis, the formation of the cells that break down bone.
MSCs can also come from bone marrow or fat tissue. Cord blood MSCs (hUCB-MSCs), however, offer three advantages: non-invasive collection, higher growth capacity and low immunogenicity. As a result, the recipient’s immune system is less likely to recognise them as foreign. You can read more on our page about umbilical cord stem cells.
The study: nine patients over five years
This is a prospective observational follow-up focused on stem cell safety. It involved 9 patients who had taken part in the phase I CURE-iv trial. At the start of that trial, they had moderate disease activity despite methotrexate. Each one received a single intravenous infusion of hUCB-MSCs at one of three doses: 25, 50 or 100 million cells.
During the follow-up, the researchers gave no new treatment. Instead, they tracked the patients over time with check-ups, lab tests and regular electrocardiograms. The goal was to record all adverse events, both serious and non-serious.
In particular, the team watched for “events of special interest”: serious and opportunistic infections, major cardiovascular events, thromboembolic events and malignancies.
Stem cell safety: the five-year results
Over five years of observation, the study recorded no deaths, no thromboembolic events and no malignancies. For research on stem cell safety, this is the central finding.
In total, the researchers counted 97 adverse events. The most common were osteoarthritis and nasopharyngitis. Four in nine patients (44.4%) reported them, and doctors expect these conditions in this age group and clinical population.
The study also reports some serious adverse events. However, clinicians judged them unrelated to the infusion:
- a case of infectious cellulitis more than a year later, which cleared with antibiotics;
- an episode of heart failure years later, attributable to pre-existing hypertension;
- two benign tumours (an ovarian tumour and a breast adenoma) three years after treatment, with no clear causal link.
Lab values also stayed stable, with just two mild, short-lived exceptions: raised triglycerides and one case of eosinophilia. Both then resolved on their own.
Efficacy: a benefit that fades over time
On efficacy, however, the picture is less clear-cut and calls for precision.
The researchers measured disease activity with the DAS28 score. After the infusion, the score fell sharply and reached its lowest values between months three and six. In general, the improvement lasted up to one year. Over the rest of the follow-up, however, the effect gradually faded and disease activity returned towards baseline.
The conclusion is clear: a single dose is not enough to change the course of a chronic disease for good. Keeping symptoms under control will probably require repeated doses. Their safety profile, however, will need dedicated studies.
The limitations the authors acknowledge
The authors are clear about three limitations:
- Very small sample. Nine patients are too few to detect rare side effects or to generalise the results.
- No control group. Without a placebo arm, it is hard to tell events caused by the therapy from those due to age or the natural course of the disease.
- Single dose. The study says little or nothing about stem cell safety with repeated doses, which is the more likely clinical scenario.
Even so, the study has one important merit. Its five years of follow-up rank among the longest ever documented for this therapy. In a field where long-term stem cell safety data are scarce, this work therefore becomes a reference point.
Important note The applications described belong to clinical research and are not approved therapies in current practice. None of the information provided constitutes medical advice.
Why SSCB follows stem cell safety research
Ultimately, long-term safety data decide whether a cell therapy can enter clinical practice. Yet stem cell safety begins long before the infusion. It depends on every step the sample goes through: collection, processing, characterisation and storage.
The FACT-NetCord standards govern exactly this chain. SSCB has held this accreditation for over twelve years, uniquely in Switzerland. In particular, the standards set minimum thresholds for total nucleated cells and CD34+ cells, viability requirements and storage at or below -150 °C. They also require ISBT 128 traceability, which hospitals worldwide recognise.
We followed the same journey from cell to patient in our article on the three requirements advanced cell therapies must meet.
Want to understand why not all biobanks are alike? Discover SSCB’s certifications and what they mean for sample quality.
Source: Park EH, Kim MJ, Kang KS, Shin K. Long-term safety of intravenous human umbilical cord blood-derived mesenchymal stem cell therapy in rheumatoid arthritis: a 5-year follow-up study. Stem Cells Transl Med. 2026;15(8):szag062. doi:10.1093/stcltm/szag062
