The Phenotype and Secretory Activity of Adipose-Derived Mesenchymal Stem Cells (ASCs) of Patients with Rheumatic Diseases

Abstract

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.

Modulation of T-Cell Activation Markers Expression by the Adipose Tissue–Derived Mesenchymal Stem Cells of Patients with Rheumatic Diseases

“…Although preconditioning can alter various MSCs activities, its final outcome depends on the type of applied priming factor and combination of some of them, e.g., TNFα and IFNγ exerts usually additive effects 41 . We have previously reported that TI treatment upregulates ICAM-1, but not VCAM-1, expression on ASCs and increases secretion of some (kynurenines, IL-6, and LIF), while fails to modify release of other (IL-1Ra, sHLA-G, TSG-6, galectin-3, and TGFβ) immunoregulatory factors, pointing out some selectivity of TI priming 10 . Importantly, untreated (naïve) MSCs are endowed with some immunoregulatory activities as well, including regulation of T-cell activation markers expression 44 , 46 , 47 , 48 .…”

“…Thus, MSCs use various mediators to keep T-cell activation under control. Identification of factors implicated in presently observed ASCs effects exerted on T lymphocytes requires further studies, but our previous comparative characteristics of HD/ASCs and RD/ASCs secretory activity point out some candidates, including TGFβ 10 .…”

“…Therefore, it is proposed that in RD adipose tissue–derived MSCs (ASCs) may represent an optional pool of therapeutically useful autologous MSCs, but biology of these cells is poorly understood 9 . We have recently reported certain abnormalities of ASCs of SLE, SSc, and AS patients in the secretory activity and expression of surface molecules (CD90, ICAM-1, and VCAM-1) 10 . Thus, it is likely that in RD prolonged chronic inflammation, irrespective of the initial cause(s), may affect immunoregulatory functions of ASCs as well.…”

Adipose-Derived Stromal/Stem Cells

“…This Special Issue covers research articles investigating various adipose tissues as a source for ASC isolation [ 1 , 2 , 3 ], specific cultures methods to enhance proliferation or viability [ 4 , 5 , 6 , 7 ], and the differentiation capacity [ 8 , 9 , 10 , 11 , 12 ]. Furthermore, other studies highlight aspects of various diseases [ 13 , 14 ], the immunosuppressive potential of ASCs and their derivates [ 15 ] or the in vivo tracking of transplanted ASCs [ 16 ].…”

“…A study by Plava and co-workers identified that ASCs are permanently altered in the presence of tumor breast tissue and have the potential to increase tumor cell invasive ability through the activation of epithelial-to-mesenchymal transition in tumor cells [ 13 ]. Another study characterized ASCs isolated from patients with rheumatoid arthritis and described their altered phenotype and secretory activity compared to ASCs from healthy donors [ 14 ].…”