Effects and Safety of Mesenchymal Stem Cell Intravenous Infusion in Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a chronic, immunemediated inflammatory disease that is associated with inflammation in the axial skeleton, peripheral joints and non-articular structures. Nonsteroidal anti-inflammatory drugs (NSAIDs) incontrovertibly relieve symptoms of AS and their constant use may reduce the rate of ankylosis. 

However, some patients have a poor response to these medications and they are associated with gastrointestinal and cardiovascular toxicity. 

The introduction of tumor necrosis factor (TNF) blockers to the treatment of AS has been considered the greatest breakthrough over the past 50 years, but their use can increase the risk of fungal and bacterial infections and the personal and societal financial burden has limited the availability of effective anti-TNF treatments, and even when available some patients are refractory to them too. 

Mesenchymal Stem Cells Use 

Many studies have shown that AS is an autoimmune disease. Mesenchymal stem cells (MSCs) are adult stem cells with desired properties for cell-based clinical therapies. Recent studies have proven the immunosuppressive and anti-inflammatory properties of MSCs. 

Many other studies have shown the safety and efficacy for other autoimmune mediated diseases with intravenous infusion of MSCs, including graft-versus-host disease, Crohn’s disease, multiple sclerosis, systemic lupus erythematosus and systemic sclerosis. 

Intravenously Infused MSCs Treatment

A study published in the SAGE journals by Peng Wang and colleagues evaluated the use of MSC intravenous (IV) infusion during a 20 week open-label clinical study in active ankylosing spondylitis patients who had a suboptimal response to, or could not tolerate the side effects of NSAIDs. 

The research included 31 patients with AS diagnosis. 22 of them had a suboptimal response to NSAIDs and 9 could not tolerate the side effects. The mean age was 27.8 years and the mean disease duration from diagnosis was 33.9 months. 

All the patients discontinued their current AS treatment for at least 72 h prior to MSC treatment to minimize the impact of their prior therapy. All patients received 1’000,000 MSCs/kg body weight in 10 ml normal saline at baseline (day 0), the first week (day 7), the second week (day 14) and the third week (day 21). Stem cells were obtained from bone marrow of 35 male donors between 20 to 30 years. 

Clinical Effects of the MSCs Treatment 

After being tested for the phenotype expression and multiple lineage differentiation potential, MSCs were intravenously infused into selected AS patients. 

The Assessment in Ankylosing Spondylitis Response Criteria (ASAS 20) was used for evaluation of the therapy. This assessment is defined as an improvement of at least 20% and an absolute improvement of at least 10 units on a 0-100 scale in at least three of the criterias, which are: patient global assessment, pain assessment, function and inflammation.  

The percentage of ASAS20 responders at the fourth week was 77.4% (24/31). ASAS Response Criteria were achieved by 2 patients (6.5%) at the first week, 13 patients (41.9%) at the second week, 19 patients (61.3%) at the third week, 21 patients (66.7%) at week eight. The mean response duration was 7.1 weeks after MSC IV infusion. 

Conclusions of the Study 

This is the first study assessing the efficacy of MSC infusion for the treatment of AS. Their results showed that MSC infusion resulted in an improvement of ASAS scores and symptoms and that the results lasted for up to 7 weeks post-treatment. No significant deteriorations were found in all tests and radiological examinations in all patients, indicating the safety of the treatment over a 20 week period. 

They observed improvement in patient symptoms, decrease CRP and ESR (inflammatory markers) and reduction of inflammation by MRI that suggest that MSC infusion is effective in the treatment of patients with AS. 

Source: 

Wang P, et al. Effects and safety of allogenic mesenchymal stem cell intravenous infusion in active ankylosing spondylitis patients who failed NSAIDs: a 20-week clinical trial. Cell Transplant. 2014;23(10):1293-303. doi: 10.3727/096368913X667727. Epub 2013 May 22. PMID: 23711393.

Image from: https://curearthritis.org/ankylosing-spondylitis/