Mesenchymal Stem Cell-Based Therapy For Rheumatoid Arthritis

Mesenchymal stem cells (MSCs) have demonstrated the ability to differentiate into a number of different cells; they also demonstrate immunomodulatory properties that have great potential for use as a stem cell-based therapeutic treatment option and for the treatment of autoimmune diseases – including rheumatoid arthritis (RA).

RA is a chronic and debilitating inflammatory disorder that not only affects the joints, muscles, and tendons, but also damages a number of other body systems, including the eyes, skin, lungs, heart, and blood vessels^[1]. It is estimated that roughly 1.5 million Americans are afflicted by RA.  While the exact cause of RA is not yet fully understood, the condition is one of over 80 known autoimmune diseases occurring as a result of the immune system mistakenly attacking the body’s own healthy tissue.

Current treatment of RA primarily involves the use of steroids and antirheumatic drugs used primarily to manage associated symptoms of the condition, rather than treat the condition itself.  These drugs are also commonly associated with a number of unwanted side effects with users often developing resistance to the medication after prolonged use.

Considering the relative ineffectiveness of drugs designed to treat RA and RA-associated symptoms, scientists have turned to investigate the use of MSC-based therapy as a potential treatment for RA.

As part of this investigation, Sarsenova et al. examined both conventional and modern RA treatment approaches, including MSC-based therapy, by examining the connection between these stem cells and the innate and adaptive immune systems. This review also evaluates recent preclinical and clinical approaches to enhancing the immunoregulatory properties of MSCs.

Through a number of in vitro studies, researchers have realized that MSCs have the ability to inhibit the proliferation of effector memory T cells which, in turn, prevents the proliferation of inflammatory cytokine production. Additionally, these studies have also demonstrated that MSCs are able to modulate functions of the innate immune system by inducting the inflammatory process and activating the adaptive immune system.

Preclinical studies have demonstrated the ability of MSCs to suppress inflammation both through interactions with cells of the immune system and through paracrine mechanisms. This has been demonstrated to be very important as cells of the innate immune system have been shown to have an important role in both the development and progression of RA.

While a number of clinical studies evaluating the effectiveness of MSC-based therapies for the treatment of RA were still ongoing at the time of publication, the nine completed studies primarily demonstrated that using MSCs for the treatment of RA is safe, well tolerated in both the short and long-term, and provides clinical improvements in RA patients.

Despite the many positive and promising outcomes observed through these clinical trials, the authors of this review also point out some limitations associated with the treatment of RA with MSCs. These limitations include many of the referenced studies lacking a placebo control, low enrollment in some studies, and a lack of optimal protocol (for both MSC sourcing and route of administration) for RA treatment with MSCs.  

Considering these limitations, Sarsenova et al. point out the need for more well-defined and effective therapeutic windows for the treatment of RA with MSCs, including MSC priming to promote an anti-inflammatory phenotype, in a future study as a way to better understand the perceived benefits of a stem-cell therapy for the treatment of RA and other autoimmune diseases.

Source: “Mesenchymal Stem Cell-Based Therapy for Rheumatoid Arthritis.” 27 Oct. 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584240/.

^[1] “Rheumatoid arthritis – Symptoms and causes – Mayo Clinic.” 18 May. 2021, https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648. Accessed 5 Oct. 2022.