Calcitriol Treated Mesenchymal Stem Cells Modulated Immune Response in Collagen-Induced Rheumatoid Arthritis in BALB/c Mice.

Abstract

Background and aim: Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily involves synovial joints. During the past decade, disease-modifying antirheumatic drugs and biologic agents have been introduced for the treatment of RA. However, they have limitations, including incomplete treatment response, adverse effects requiring drug withdrawal, fall off in efficacy over time, high cost of biologic agents, and refractory cases. Consequently, there is a need to establish safe and effective advanced therapeutic modalities for RA to overcome the shortcomings of current treatments.

Methods: MSCs after isolation were exposed to 200 nM calcitriol. Rheumatoid arthritis was induced in BALB/c mice using collagen and Freund's complete adjuvant. One week after immunization, the mice were divided into 3 groups including without treatment, groups treated with untreated and treated MSCs. One week after the last injection, mice sacrificed and samples were taken and the desired evaluations were done.

Results: Our results revealed that the respiratory burst capacity, neutrophil phagocytosis, and nitric oxide production in the population of splenocytes were higher in the positive control group compared to the treatment groups. Also, the level of production of IL-4, IL-10 and TGF-β cytokines and INF-γ and IL-17 cytokines showed a significant increase and decrease, respectively, compared to the positive control group.

Conclusion: Treatment of MSCs with calcitriol leads to an improvement in regulatory function and inhibitory effects on inflammatory mediators of innate immune cells, particularly splenocytes, in a rheumatoid arthritis model compared to untreated mesenchymal stem cells.