Mesenchymal stem/stromal cells (MSCs) have immunosuppressive and regenerative properties. Adipose tissue is an alternative source of MSCs, named adipose-derived mesenchymal stem cells (ASCs). Because the biology of ASCs in rheumatic diseases (RD) is poorly understood, we performed a basic characterization of RD/ASCs. The phenotype and expression of adhesion molecules (intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1) on commercially available healthy donors (HD), ASC lines (n = 5) and on ASCs isolated from patients with systemic lupus erythematosus (SLE, n = 16), systemic sclerosis (SSc, n = 17) and ankylosing spondylitis (AS, n = 16) were analyzed by flow cytometry. The secretion of immunomodulatory factors by untreated and cytokine-treated ASCs was measured by ELISA. RD/ASCs have reduced basal levels of CD90 and ICAM-1 expression, correlated with interleukin (IL)-6 and transforming growth factor (TGF)-β1 release, respectively. Compared with HD/ASCs, untreated and tumour necrosis factor (TNF) + interferon (IFN)-γ (TI)-treated RD/ASCs produced similar amounts of prostaglandin E2 (PGE2), IL-6, leukemia inhibiting factor (LIF), and TGF-β1, more IL-1Ra, soluble human leukocyte antigen G (sHLA-G) and tumor necrosis factor-inducible gene (TSG)-6, but less kynurenines and galectin-3. Basal secretion of galectin-3 was inversely correlated with the patient’s erythrocyte sedimentation rate (ESR) value. IFN-α and IL-23 slightly raised galectin-3 release from SLE/ASCs and AS/ASCs, respectively. TGF-β1 up-regulated PGE2 secretion by SSc/ASCs. In conclusion, RD/ASCs are characterized by low basal levels of CD90 and ICAM-1 expression, upregulated secretion of IL-1Ra, TSG-6 and sHLA-G, but impaired release of kynurenines and galectin-3. These abnormalities may modify biological activities of RD/ASCs.

Objectives. To evaluate the chondrogenic potential, phenotype and percentage of IA adipose-derived mesenchymal stem cells (ADSCs) from RA patients in comparison with OA patients. The effect of TNF treatment on ADSC differentiation was also examined. Methods. Adipose tissue was obtained from RA and OA patients. ADSCs were isolated and cultured until passage 4. After that period, the phenotype and percentage of these cells were analysed by flow cytometry. Passage 4 cells were cultured in chondrogenic medium with or without TNF. After 3 weeks of differentiation the expression of Sox9, aggrecan (Acan) and collagen 2a (Col2a) mRNA was assessed by RT-PCR and GAG deposition by alcian blue staining. Results. The phenotype and percentage of ADSCs were similar in both RA and OA. The results of alcian blue staining showed effective chondrogenesis in RA and OA ADSCs. TNF inhibited GAG deposition in both RA and OA samples similarly. Sox9, Acan and Col2a mRNA expression was significantly increased in chondrogenic-medium-treated cells (P < 0.05) and decreased after TNF exposure (P < 0.01). No statistically significant differences between RA and OA were observed. Conclusion. ADSCs from RA and OA patients are similar with regard to their phenotype, percentage in IA tissue and chondrogenic potential, which is reduced after exposure to TNF.

Adipose-derived mesenchymal stem cells (ASCs) possess immunosuppressive properties, but their activity is dependent on stimuli provided by local environment. It is possible that proinflammatory milieu of rheumatoid joint affects ASCs function. To verify this hypothesis, rheumatoid ASCs (RA-ASCs) and osteoarthritic ASCs (OA-ASCs) derived from infrapatellar fat pad (IPFP) of the knee joint have been compared. RA- and OA-ASCs isolated from patients were cultured in vitro. Their secretory and proliferative activity was measured. Peripheral blood mononuclear cells (PBMCs) from healthy donors were co-cultured with ASCs. Then, PBMCs proliferation was measured by (3)H-thymidine incorporation method, cytokines secretion by immunoassays, T cells activation and regulatory T cells (Tregs) percentage - by flow cytometry. RA- and OA-ASCs properties in vitro were comparable, however, some differences in secretory activity occurred. RA- and OA-ASCs inhibited PBMCs proliferation and induced interleukin 10 production but up-regulated interleukin 17 A secretion and failed to limit release of other proinflammatory mediators (tumor necrosis factor [TNF], interferon γ [IFNγ], CCL5) by PBMCs. RA- and OA-ASCs did not suppress activation markers expression on T cells and did not trigger Tregs expansion. The present study shows that IPFP-ASCs from RA and OA patients have comparable functions in vitro. Their immunosuppressive activity seems to be impaired comparing to available data.

In the general population, low-grade inflammation of adipose tissue accompanies obesity and contributes to cardiovascular disease (CVD) development, but the implication of this tissue in rheumatic disease pathology is unclear. Therefore, we characterized the secretory activity of subcutaneous abdominal adipose tissue (SAAT) of females with rheumatoid arthritis (RA) and osteoarthritis (OA) and searched for its relationship with intensity of systemic inflammation, body composition and comorbidity. The secretion of classical adipokines (leptin, adiponectin), pro- and anti-inflammatory factors, i.e. interleukin (IL)-6, IL-8, IL-10, tumour necrosis factor (TNF), macrophage migration inhibitory factor (MIF) and hepatocyte growth factor (HGF), from SAAT explants was measured by specific enzyme-linked immunosorbent assays. Patients' body composition was evaluated by bioelectric impendence technique. Rheumatoid SAAT secreted more adiponectin, IL-6, IL-10, TNF and MIF but less leptin than respective osteoarthritis tissues. In RA patients, TNF secretion correlated with cachectic body composition, HGF release was linked to secondary amyloidosis and visceral fat rating was an independent risk factor for CVD. In OA, secretion of leptin and HGF positively, while adiponectin inversely, correlated with systemic inflammation markers, and the release of MIF was an independent risk factor for CVD. This study reveals differences between RA and OA patients in SAAT secretory activity and suggests its different clinical impact in these diseases, characterized by high- and low-grade systemic inflammation, respectively. In RA, SAAT may directly or via an effect on body composition contribute to amyloidosis, cachexia or CVD co-occurring, while in OA SAAT-derived adipocytokines may rather regulate intensity of systemic inflammation and redound to CVD emergence.

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