Ankylosing Spondylitis and Mesenchymal Stem Cell Treatment

What is Ankylosing Spondylitis? 

Ankylosing spondylitis (AS) is a chronic progressive spinal inflammatory arthritis and belongs to the spondyloarthropathies (SpA) group. The clinical manifestations usually emerge in the third decade of life. 

AS typically affects the sacroiliac joints, axial skeleton, entheses (tendon or ligament attachments to bone) and extra-skeletal sites such as the eye, bowel and skin can be frequently affected. 

It can lead to bone erosion, new bone formation and ankylosis occurring in the spine, which leads to severe pain, a reduction in spinal mobility and stiffness. 

Over time the disease can cause the spine (vertebrae) to fuse, which makes the spine less flexible and result in a hunched-forward posture. If ribs are affected, it can be difficult to breathe deeply. 

Epidemiology 

AS has an average prevalence of 16.7 in Asia, 23.8 in Europe and 31.9 in North America and 10.2 in Latin America per 10,000 individuals. 

There is also a gender difference in AS patients between continents and countries. Globally, the gender ratio (male:female) is 2.5:1. 

What Causes AS? 

It has no known specific cause, though genetic factors seem to be involved. In particular, people who have a gene called HLA-B27 are at a greatly increased risk of developing ankylosing spondylitis. 

It has been suggested that cellular elements and cytokine networks, especially the Interleukin-23 (IL-23)/IL-17 pathway, involved with innate and adaptive immunity are closely associated with triggering, initiation and progression of the disease inflammation, both acute and chronic. 

What are Common Symptoms of AS? 

Early signs and symptoms of AS might include pain and stiffness in the lower back and hips, especially in the morning after periods of inactivity. Neck pain and fatigue are also common. Over time, they might worsen, improve or stop at irregular intervals. 

Current Treatment Options 

Current drug therapy options are focused on reducing inflammation, stiffness, back pain and disability. 

The treatments include non-steroidal antiinflammatory drugs (NSAIDs), disease modifying anti-rheumatic drugs (DMARDs) and biologic agents, including tumor necrosis factor (TNF) and IL-17 A blockers. 

These therapies can reduce inflammation and improve clinical manifestations and AS quality of life. However, many patients suffer from unresponsive or unbearable side effects from the drugs. 

The use of TNF-α inhibitors is the best choice in patients who poorly respond to other treatments. Four synthetic anti-TNF-α agents, including infliximab (Remicade), adalimumab (Humira, golimumab (Simponi) and the recombinant receptor etanercept (Enbrel) are currently used in order to decrease signs of spinal inflammation and seem to improve imaging outcomes. 

A big obstacle is that almost 40% of AS patients are unable to tolerate or respond to conditional medications. In a proportion of them with inadequate response to first anti-TNF therapy, alternative TNF-α inhibitors will be used, and despite switching there is still a chance of failure because of drug inefficacy or possible side effects. 

Given that there is no cure for the disease, the use of stem cell therapy has the promise to raise hope as a good and beneficial treatment option. 

Mesenchymal Stem Cells 

Mesenchymal stem cells (MSCs) are a kind of stem cells that can revolutionize medicine due to their multipotent capacity and immunomodulatory properties. These cells can migrate to the site of inflammation and injury, where they could apply antiinflammatory and repairing effects. 

Bone marrow is the primary source for harvesting MSCs;furthermore, umbilical cord and adipose tissue are the other main source of these cells.

MSCs induce an inhibitory environment through inhibition by cell-to-cell contract and soluble factor secretion. Numerous studies have shown that MSCs possess immunomodulatory effects. Secretion of many biological molecules and mediators, such as cytokines. 

MSCs have low immunogenicity due to the absence of cell surface HLA-DRa. In this way, MSCs can affect immune function of cells and exert the immunosuppressive effects, and these properties can confer many therapeutic benefits of MSC transplantation in diseases. 

MSCs produce many molecules in response to stimulants, such as hypoxia, and inflammatory stimulants (IFN-γ, TNF-α, LPS). These stimulants can affect the secretion levels of these molecules and have effects on the immune system regulation. 

Advantages of MSCs for AS Treatment

1. Accessibility (Umbilical cord, bone marrow, adipose tissue…)
2. Easy to harvest and expand in tissue culture. 
3. Immunosuppressive effects.
4. Multi-lineage differentiation (regenerative effects).
5. Favorable therapeutic choice for transplantation.

The safety and therapeutic potency of MSC therapy have been shown in many types of research, and also in other disorders such as SLE, MS and autoimmune diseases.

Previous reports have shown that the number of Treg cells in AS patients are low, as well as low levels and abnormal function of B cells, with the resulting auto-antibodies being involved in AS pathogenesis. 

MSCs can differentiate T cells to Th2 cells and decrease pro-inflammatory cytokine levels and therefore decrease inflammation and benefiating AS patients. 

Previous studies have shown that MSC infusion in AS patients is a safe and beneficial choice with no severe side effects, and is effective in decreasing the related clinical symptoms and severity of the disease. 

Clinical Trials 

Wang et al. demonstrated that intravenous infusion of allogeneic mesenchymal stem cells is an effective and safe treatment in active ankylosing spondylitis patients. Also, in a study conducted by Ai Li et al. the intravenous transfusion of umbilical cord mesenchymal stem cells (UC-MSCs) shows beneficial outcomes such as safety and decrease of clinical symptoms in AS patients. Multiple clinical trials are in progress for treating AS patients with MSCs due to the incredible properties of the cells and the favorable results seen in previous trials. 

MSCs Treatment at Zignagenix 

In our clinic we are offering this cellular therapy using MSCs derived from the Warthon’s jelly umbilical cord. We use a combined therapy with high doses of MSCs given intravenously (IV) and exosomes also given IV, and depending on the patient affected area, localized injections at the level of the facet joints of the spine and the sacroiliac joints. 

We also combine our localized injections with Platelet-Rich Plasma because it also has different antiinflammatory cytokines and growth factors that help modulate the immune response and increase the regenerative potential of the therapy. 

Sources: 

Kamal Abdolmohammadi, et al. Ankylosing spondylitis and mesenchymal stromal/stem cell therapy: a new therapeutic approach. Biomedicine & Pharmacotherapy, Volume 109, 2019. ISSN 0753-3322. https://doi.org/10.1016/j.biopha.2018.10.137. 

https://www.mayoclinic.org/diseases-conditions/ankylosing-spondylitis/symptoms-causes/syc-20354808

Images from: 

https://www.healthdirect.gov.au/ankylosing-spondylitis