Marie Trudelle

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of joint synovium, leading to irreversible joint destruction¹. The disease affects about 1.4 million Americans and over 25 million individuals worldwide, with higher rates observed in Native American populations and a prevalence 2.5 times that of men found in women¹. Genetics, smoking, and gender have been determined to be significant risk factors for rheumatoid arthritis¹. RA namely affects small joints, usually in the hand and feet, but can also lead to heart, lung, eye, and kidney complications¹. Mesenchymal stem cells (MSCs) are multipotent cells, meaning they can differentiate into different cell types, making them a potential tool for therapy of inflammatory disease². MSCs have been shown to have an anti-inflammatory and immunoregulatory actions in autoimmune disorders, but their mechanism of action in modulating RA inflammation and joint destruction is poorly understood^3,4. Methods: This study gathered information from previous research studies ranging from year 2013 to 2018. Mechanistic research on rheumatoid arthritis typically utilizes collagen-induced arthritis (CIA) mice, developed according to recognized procedures. CIA is induced by extracting type II collagen (CII) from bovine, murine, or chicken cartilage^3,4,5,6. CII is purified and emulsified with complete Freund’s adjuvant (CFA) and injected into the mice at the base of the tail^3,4,5,6. Extraction of MSCs is much more varied between research studies because it can be obtained from several different tissues and sources. Criteria for MSCs is multipotency potential and expression of CD105, CD73, and CD90 markers with absence of endothelial and hematopoietic markers⁷. Results: Results from this research yielded information of the mechanism of disease pathogenesis in RA and the role of MSCs in modulating inflammation in autoimmune diseases. The activity of MSCs in RA is evaluated via histopathological evaluation of the joints, flow cytometry, cytokine analysis, and in vitro assays^5,6. The collected data is then statistically analyzed for significance. Conclusion: Studies have found that MSCs are successful in regulating autoimmunity and chronic inflammation, demonstrating their therapeutic potential in RA. Several likely mechanisms have been identified, including cell-cell contact dependent interaction and soluble cytokine contact-independent interactions^3,4,5. More research needs to be done to fully understand the mechanisms of MSC immunoregulation in RA.

1. Smolen JS, Aletaha D, Barton A, et al. Rheumatoid arthritis. Nature Reviews Disease Primers. 2018;4:18001.
2. Castro-Manrreza ME, Montesinos JJ. Immunoregulation by mesenchymal stem cells: biological aspects and clinical applications. J Immunol Res. 2015;2015:394917.
3. Garimella MG, Kour S, Piprode V, Mittal M, Kumar A, Rani L, Pote ST, Mishra GC, Chattopadhyay N, Wani MR. Adipose-Derived Mesenchymal Stem Cells Prevent Systemic Bone Loss in Collagen-Induced Arthritis. J Immunol. 2015;195(11):5136-48.
4. Park KH, Mun CH, Kang MI, Lee SW, Lee SK, Park YB. Treatment of Collagen-Induced Arthritis Using Immune Modulatory Properties of Human Mesenchymal Stem Cells. Cell Transplant. 2016;25(6).
5. Chen M, Su W, Lin X, Guo Z, Wang J, Zhang Q, Brand D, Ryffel B, Huang J, Liu Z, He X, Le AD, Zheng SG. Adoptive transfer of human gingiva-derived mesenchymal stem cells ameliorates collagen-induced arthritis via suppression of Th1 and Th17 cells and enhancement of regulatory T cell differentiation. Arthritis Rheum. 2013;65(5):1181-93.
6. Sun Y, Kong W, Huang S, Shi B, Zhang H, Chen W, Zhang H, Zhao C, Tang X, Yao G, Feng X, Sun L. Comparable therapeutic potential of umbilical cord mesenchymal stem cells in collagen-induced arthritis to TNF inhibitor or anti-CD20 treatment. Clin Exp Rheumatol. 2017;35(2):288-295.
7. Franceschetti T, De Bari C. The potential role of adult stem cells in the management of the rheumatic diseases. Ther Adv Musculoskelet Dis. 2017;9(7):165-179.