Rheumatoid arthritis is the most common inflammatory arthritis disease worldwide and is a major cause of disability. It existed in early Native American populations several thousand years ago but might not have appeared in Europe until the 17th century. Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the accumulation of inflammatory cells into the synovium (joint lining) and the destruction of joints. 

Clinical Signs  

Symmetrical inflammatory polyarthritis is the primary clinical manifestation. The arthritis usually begins in the small joints of the hands and the feet, spreading later to the larger joints. The inflamed joint lining (synovium) extends and then causes erosion initially of the cartilage and then of the bone leading to joint destruction, deformity and subsequent disability. If erosions occur in RA (majority of cases) they will do so in the first one or two years and possibly earlier.

Extra-articular features include nodules, pericarditis, pulmonary fibrosis, peripheral neuropathy and amyloidosis.

Treatment

There is no cure for RA. Drug treatment falls into five categories:

1. Non-steroidal anti-inflammatory drugs - of which the cheapest is aspirin - which relieve pain and stiffness.

2. Second-line agents such as injectable gold, methotrexate and sulphasalazine - which slow the disease process and reduce the acute phase response. They have  high side-effects and require careful monitoring.

3. Steroids - which produce symptomatic benefit, require no monitoring, but have serious long- term consequences.

4. Immunosuppressive drugs - which are needed for the small proportion of patients with systemic disease.

5. The new biologic agents - directed against inflammatory cytokines. The exact place of these agents in the treatment of RA has yet to be established

In addition to drug treatment, orthopedic surgery is able to offer great relief to those particularly in the second and third decade of disease, who have been severely disabled. Physiotherapy and adaptations to the home may also reduce disability. It is estimated that, with current management applied optimally, the burden of disability due to RA might be further reduced by 25% in developed countries. There is some recent evidence that methotrexate may reduce mortality 

In low income countries, the appropriate infrastructure to provide adequate supervision of second- line drug therapy; and to provide skilled orthopaedic surgery is often absent. In addition, steroid therapy is often freely available and used indiscriminately. Thus it is estimated that the burden of disability due to RA might be reduced by 40% if medical input were increased. 

Due to the inability of RA sufferers to contribute to the workforce in any pain free manner, the cost of care on the public purse over the long course of the disease is great.

The use of medical therapies ( Non steroidals, corticoids and immunosuppressives), there have been uncertainties in efficacy and long-term safety

Cell and Cytokine therapy

1. Cellular Therapies 

A number of trials using mesenchymal stem cells derived from human Umbilical cord blood have been trialled both in vivo and in vitro to good long term effect. Mesenchymal stem cells (MSCs) have been suggested as a promising alternative for the treatment of RA because of their immunomodulatory properties. 

Mesenchymal stem cells (MSCs) are multipotent cells existing in many foetal and adult tissues that can replicate as undifferentiated cells and potentially differentiate to lineages of mesenchymal tissues.  MSCs can also modulate several immune functions through interplay with cells from both innate and adaptive immune systems.

Furthermore, after administration in vivo, MSCs can migrate to injured tissues, where they can restrain the release of pro-inflammatory cytokines and facilitate the survival of damaged cells, and also induce peripheral immune tolerance.

Clinical studies have confirmed that MSCs have clinical benefits in severe acute graft-versus-host disease and in different autoimmune diseases, such as systemic lupus erythematosus .

Previous studies found that MSCs may treat RA, and many mechanisms were explored.

2. Cytokines

Cytokines are important regulators of the synovial inflammation. Some cytokines, such as tumour necrosis factor (TNF)-α and interleukin (IL)-1, function by promoting inflammatory responses and by inducing cartilage degradation. Other cytokines, such as IL-4, IL-10 and IL-13, function mainly as anti-inflammatory molecules. Although anti-inflammatory cytokines are present in rheumatoid joints, in progressive RA their levels obviously are too low to neutralize the deleterious effects of proinflammatory cytokines.

It has been reported that pro-inflammatory cytokines and chemokines play an essential role in RA. Biological agents aiming at those cytokines have been tested clinically, such as recombinant human tumour necrosis factor (TNF) receptor-Fc fusion protein and recombinant human interleukin (IL)-1 receptor antagonist.  However, there were moderate–severe side effects observed, including relapse and an increased susceptibility to infections. It is highly unlikely that there is a single cytokine causative for RA. We suggest it is far more likely that a combination of anti-inflammatory cytokines would be able to give a positive therapeutic response in human patients over the long term.

UCF

Given the clinically positive effects in RA patients using Umbilical Cord MSCs and the fact that these cells have their therapeutic effect via the cytokine arrays they produce, we are keen to pursue a trial using the systemic (IV) application of Umbilical Cord Derived factors embodied in the Purcell UCF sterile cytokine product.

This product has already been used safely (both locally and systemically) across a range of patients-including a small number of RA sufferers- to good long term effects with no side effects.