AB0039 Immunosuppressive effect of mesenchymal stem cells on monocytes derived from patients with rheumatoid arthritis

Background Mesenchymal stem cells (MSCs) are a heterogeneous population of fibroblast-like progenitor cells that may be isolated and expanded from bone marrow, umbilical cordand other tissues. Moreover, MSCs display the capacity to self-renew and differentiate into various mesodermal cell lineages. They also have drawn considerable attention for their regenerative and immunosuppressive effects in a range of autoimmune diseases, which raises the question for their potential use as therapeutic tool in rheumatoid arthritis. Objectives In line with aforementioned and taking in mind that monocytes playing pivotal role in orchestrating immunological tolerance, we aimed to study the immunosuppressive effects of adipose tissue derived mesenchymal stem cells (AT-MSC) on monocytes derived from patients with rheumatoid arthritis (RA). Methods We enrolled 12 patients matching the ACR/ EULAR 2010 criteria for RA. AT-MSC were isolated and cultured according to well established protocols. ELISA was performed for testing the cytokines produced by AT-MSC (IL-1, IL-10, IL-4, IFN-γ, IL-6, IL-8, CCL-5, RANTES, IL-17). Peripheral blood mononuclear cells (PBMCs) isolated from RA patients’ samples were cultured in AT-MSC conditioned media and in control media. Flow cytometry was used for detection of monocytes markers (CD14, CD80, CD86, HLA-DR). Results Our results revealed considerable increase in number of cells expressing the myeloid lineage surface marker CD14 (p=0.026) under the influence of AT-MSC medium. We further demonstrated decrease in percentage values of monocytes expressing HLA-DR (p=0.004) and CD80/86 surface molecules (p=0.47). Moreover, significant reduction in mean fluorescent intensity of HLA-DR surface expression (p=0.016) was also demonstrated. Conclusions Our study unambiguously points out that under the impact of AT-MSC media monocyte development into dendritic cells was hampered and was also skewed into direction of accumulation of monocytes displaying more tolerogenic phenotype characterised by down regulation of HLA-DR and B7 complex (CD80/86) surface expression. Furthermore, antigen presentation alongside with expression of the co-stimilatory B7 complex and cytokine ambience forms a three-way signalling pathway responsible for T helper activation and proliferation and consequent antibody production by plasma cells. Hence, effects exerted by AT-MSC conditioned media on monocyte lineage development should not be neglected in the context of developing novel therapeutic approaches and strategies for treatment of RA. Disclosure of Interest None declared