Rheumatoid Arthritis (RA) is a disease that occurs when the body’s immune system– originally designed to attack and eliminate diseased, cancerous, or dead cells– begins to attack the tissues of the body instead. This affects the joints, and can eventually bring detriment to other body organs as well. Because it is the result of a dysfunction of the immune system, it is referred to as an autoimmune or immunological disease.
Mesenchymal stem cells (MSCs) are, in theory, very well suited for RA therapies as they have been found to have immunosuppressive qualities (slowing down or hindering the immune system) as well as restorative qualities that can potentially help joints ravaged by this disease.
The following study takes a look at the immunological aspect of MSC therapy.
Using MSCs from Umbilical Cord Blood to Fight the Immunological Aspects of Rheumatoid Arthritis.
In a study published on December 22, 2016 in Cell Death & Disease, entitled “Human umbilical cord blood-stem cells direct macrophage polarization and block inflammasome activation to alleviate rheumatoid arthritis”, researchers attempted to investigate the therapeutic potential of human umbilical cord blood-derived MSCs (hUCB-MSCs) as an RA therapy, and to better understand the mechanisms behind hUCB-MSC-mediated impacts on the immune system.
The study, which was conducted on mice using human stem cells, found that even a single injection of hUBC-MCSs reduced the immune dysfunctions responsible for causing damage, as well as attenuating the damage itself (pannus formation, synovitis and cartilage destruction).
The study noted that similar research conducted with MSCs from bone marrow did not produce the same results.
Since the study was conducted on mice who had a type of disorder (very similar in manifestation to RA) that could be induced, rather than RA itself, and since the research was not yet developed for human subjects, much remains to be accomplished. Still the results were very promising, produced significant improvement, and the mice suffered no ill side-effects.
Follow the link to read this article for yourself.
Using Umbilical Cord Derived Mesenchymal Stem Cell for Juvenile Idiopathic Arthritis Therapy
A study published in 2016 in Stem Cells International entitled “Clinical Observation of Employment of Umbilical Cord Derived Mesenchymal Stem Cell for Juvenile Idiopathic Arthritis Therapy” also explored the use of umbilical cord derived MSCs, this time on a group 10 human subjects with juvenile idiopathic arthritis.
Juvenile idiopathic arthritis is also known as Juvenile rheumatoid arthritis. It is the most common type of arthritis among children. The goal of this study was to observe the results when juvenile idiopathic arthritis patients were given two injections of human umbilical cord derived MSCs. These injections were spaced three months apart. Immune system and joint function were evaluated at three months, and again at six months.
The results were very encouraging. Steroid and and NSAID use decreased, immune system markers were closer to normal levels, and joint function had improved.
This study demonstrated that UC-MSC therapy could reduce pain in JIA patients and improve immune function.
Subjects did not experience negative side effects, and long term efficacy was confirmed after 1 and 2 year follow up.
Follow the link to read this article for yourself
Exploring Challenges in MSC Therapy for Rheumatoid Arthritis
The following study explores a perplexing challenge in stem cell therapy for rheumatoid arthritis– the similarities of fibroblast-like synoviocytes (FLSs) and mesenchymal stem cells (MSCs).
The study was published in the May 1, 2015 edition of Arthritis Research and Therapy, in an article titled “Are mesenchymal stem cells in rheumatoid arthritis the good or bad guys?”
Fibroblasts are cells in the connective tissues of animals whose intended function is to produce the structural framework (stroma) for animal tissues, and play a critical role in wound healing. While Fibroblast-like synoviocytes are also a part of the stroma (structure) of the intimal lining (aka synovium, or synovial membrane) of synovial joints (neck, vertebrae, shoulder, elbow, wrist, hip, pelvis, knee and ankle), they produce cytokines, a category of small proteins that function as signaling molecules to mediate and regulate immunity, inflammation and the production of blood platelets in the bone marrow. These cytokines perpetuate inflammation and proteases that contribute to cartilage destruction. The FLSs of people with Rheumatoid arthritis (RA) are particularly aggressive and invasive, and intensify joint damage.
There was quite a bit of excitement when it was discovered recently that MSCs with the ability to differentiate into cartilage are present in joint tissues. At first glance this would seem to create the possibility for treatment by targeting MSC repair mechanisms. This is much needed, because even when RA is in clinical remission, joint damage may continue.
But this study concluded the distinction of MSCs and FLSs are not as clearly defined as was hoped.
In normal conditions, MSCs in the joint are believed to contribute to the maintenance and repair of joint tissues. In rheumatoid arthritis however, the repair function of MSCs appears to be repressed. It is a possibility that MSCs could instead interact with the immune system in a way that perpetuates the joint damage and the disease, rather than restoring balance.
However, the study did cite a case in which cultured, umbilical cord derived MSCs injected intravenously in combination with disease-modifying antirheumatic drugs (DMARDs) produced a significant improvement compared to the control group who received only DMARDs.
In the end it was concluded that MSCs have the potential to be used therapeutically, but elucidation of the relationship between MSCs and FLSs is a scientific necessity. Much greater understanding is needed.
Follow the link to read this fascinating study for yourself. https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-015-0634-1