scholarly journals Mesenchymal Stem Cells from Patients with Rheumatoid Arthritis Display Impaired Function in Inhibiting Th17 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Yue Sun ◽  
Wei Deng ◽  
Linyu Geng ◽  
Lu Zhang ◽  
Rui Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Th17 Cell ◽  
Mononuclear Cells ◽  
Biological Activities ◽  
Treg Cells ◽  
Cell Polarization ◽  
Peripheral Blood Mononuclear ◽  
Tfh Cells

Mesenchymal stem cells (MSCs) possess multipotent and immunomodulatory properties and are suggested to be involved in the pathogenesis of immune-related diseases. This study explored the function of bone marrow MSCs from rheumatoid arthritis (RA) patients, focusing on immunomodulatory effects. RA MSCs showed decreased proliferative activity and aberrant migration capacity. No significant differences were observed in cytokine profiles between RA and control MSCs. The effects of RA MSCs on proliferation of peripheral blood mononuclear cells (PBMCs) and distribution of specific CD4+T cell subtypes (Th17, Treg, and Tfh cells) were investigated. RA MSCs appeared to be indistinguishable from controls in suppressing PBMC proliferation, decreasing the proportion of Tfh cells, and inducing the polarization of Treg cells. However, the capacity to inhibit Th17 cell polarization was impaired in RA MSCs, which was related to the low expression of CCL2 in RA MSCs after coculture with CD4+T cells. These findings indicated that RA MSCs display defects in several important biological activities, especially the capacity to inhibit Th17 cell polarization. These functionally impaired MSCs may contribute to the development of RA disease.

scholarly journals Check-control of inflammation displayed by bone marrow mesenchymal stem cells in rheumatoid arthritis patients

Immunotherapy ◽  
2019 ◽  
Vol 11 (13) ◽  
pp. 1107-1116 ◽  
Author(s):  
Jose R Lamas ◽  
Arkaitz Mucientes ◽  
Cristina Lajas ◽  
Benjamín Fernández-Gutiérrez ◽  
Yaiza Lópiz ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
T Cell Activation ◽  
Repeated Measures ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Musculoskeletal Diseases ◽  
Peripheral Blood Mononuclear

Background: Mesenchymal stem cells (MSCs) are a promising treatment of different musculoskeletal diseases including osteoarthritis and rheumatoid arthritis (RA). Results from different approaches in this treatment have been not conclusive. Aim: To analyze factors related to interactions between peripheral blood mononuclear cells (PBMCs) and MSCs and the influence of cellular activation. Materials & methods: PBMCs from RA patients and healthy controls (HC) were obtained. MSCs from bone marrow (BM-MSCs) were obtained from six donors. CD4, CD25, CD69 and CD127 expression was measured by flow cytometry. Repeated measures analysis of variance (ANOVA) models were performed using activation, co-culture with BM-MSCs and time of culture (24 h, 72 h, 6 days) as within-subject variables. Results: PBMCs activated and co-cultured with BM-MSCs showed a lower proportion of CD25-positive and CD25high/CD127low-negative cells in both RA and HC. Additionally, a maintained expression of CD69 was also observed in RA and HC when PBMCs were activated and co-cultured with BM-MSCs. Conclusion: Both PBMC activation grade and RA disease activity influence the immunomodulatory effect of BM-MSCs on T-cell activation.

scholarly journals Effects exerted by mesenchymal stem cells on monocytes obtained from patients with rheumatoid arthritis and progressive systemic sclerosis

2019 ◽  
pp. 44-54
Keyword(s):  
Rheumatoid Arthritis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Mononuclear Cells ◽  
Progressive Systemic Sclerosis ◽  
Conditioned Media ◽  
Blood Monocytes ◽  
Peripheral Blood Mononuclear ◽  
Therapeutic Benefits ◽  
Hla Dr

In the context of autoimmune inflammatory diseases, the therapeutic benefits of mesenchymal stem cells (MSCs) could be found in their potential to exert immunosuppressive effects and to regulate the immune response. In pursuit of having a more complete look a the regulatory mechanisms performed by AT-MSC, we examined the influence of adipose stem cells (AT-MSC) on blood monocytes from patients with rheumatoid arthritis (RA). Comparison of the effect exerted by the soluble factors produced by AT-MSC vs. cell culture control media, on peripheral blood mononuclear cells (PBMC), showed a significant decrease in the percentage of HLA-DR expressing monocytes, 55.3% (IQR 30-65%) vs. 72% (IQR 62-81%), p = 0.001, as well as a significant decrease in mean fluorescence intensity MFI of HLA-DR was observed, 265 MFI (IQR 102-896 MFI) vs. 473 MFI IQR 160-2201 MFI), p = 0.001. The percentage of CD14 expressing monocytes and CD14 MFI, was increased in PBMC cultured with AT-MSC conditioned media as opposed to control media: 11.7% (IQR 7.6-16.5%) vs. 6.6% (IQR 4.6-11.8%), p = 0.013 and the surface expression density of CD14, 2702 (IQR 1548-3418) vs. 1540 (IQR 1146-2140), p = 0.05. sVEGF-A levels in PBMC cultures from PA patients cultured with conditioned media from AT-MSC were significantly higher than PBMC cultured with control media suppressing secretion of sVEGF-A, 5012 (IQR 2516-5054 pg/ml) vs. 561 pg/ml (IQR 288-699 pg/ml), p = 0.001.

scholarly journals Immunomodulatory Effects of Human Adipose Tissue-derived Mesenchymal Stem Cells on T Cell Subsets in Patients with Rheumatoid Arthritis

2019 ◽  
Author(s):  
Rasoul Baharlou ◽  
Nesa Rashidi ◽  
Abbas Ahmadi-Vasmehjani ◽  
Mahshid Khoubyari ◽  
Maryam Sheikh ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Transcription Factors ◽  
T Cell ◽  
Mononuclear Cells ◽  
Orphan Receptor ◽  
T Cell Subsets ◽  
Peripheral Blood Mononuclear

Adipose-derived mesenchymal stem cells (Ad-MSCs) have been reported to suppress the effector T cell responses and have beneficial effects on various immune disorders, like rheumatoid arthritis (RA). This study was designed to investigate the effects of co-cultured Ad-MSCs on peripheral blood mononuclear cells (PBMCs) of RA patients and healthy individuals, through assessing transcription factors of T cell subsets. PBMCs from RA patients and healthy donors were co-cultured with Ad-MSCs with or without Phytohaemagglutinin (PHA). The quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of T-box 21 (T-bet), GATA-binding protein-3 (GATA3), retinoid-related orphan receptor γt (ROR-γt) and forkhead box P3 (Foxp3). Based on the results, Ad-MSCs greatly upregulated Th2 and Treg cell transcription factors, i.e., GATA3 and Foxp3 (p<0.05), and downregulated Th1 and Th17 transcription factors, i.e., T-bet and RORγt (p<0.05). These results demonstrate that Ad-MSCs can result in an immunosuppressive environment through inhibition of pro-inflammatory T cells and induction of T cells with a  regulatory phenotype. Therefore, they might have important clinical implications for inflammatory and autoimmune diseases such as RA.

scholarly journals The Comparison of the Immunologic Properties of Stem Cells Isolated from Human Exfoliated Deciduous Teeth, Dental Pulp, and Dental Follicles

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Selin Yildirim ◽  
Noushin Zibandeh ◽  
Deniz Genc ◽  
Elif Merve Ozcan ◽  
Kamil Goker ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dental Pulp ◽  
Fas Ligand ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Venous Blood ◽  
Deciduous Teeth ◽  
Peripheral Blood Mononuclear ◽  
Human Exfoliated Deciduous Teeth

Aim. To compare the effects of various mesenchymal stem cells, those isolated from human exfoliated deciduous teeth (SHEDs), dental pulp stem cells (DPSCs), and dental follicle stem cells (DFSCs), on human peripheral blood mononuclear cells (PBMCs).Method. Mesenchymal stem cells were isolated from three sources in the orofacial region. Characterization and PCR analyses were performed. Lymphocytes were isolated from healthy peripheral venous blood. Lymphocytes were cocultured with stem cells in the presence and absence of IFN-γand stimulated with anti-CD2, anti-CD3, and anti-CD28 for 3 days. Then, lymphocyte proliferation, the number of CD4+FoxP3+T regulatory cells, and the levels of Fas/Fas ligand, IL-4, IL-10, and IFN-γin the culture supernatant were measured.Results. The DFSCs exhibited an enhanced differentiation capacity and an increased number of CD4+FoxP3+T lymphocytes and suppressed the proliferation and apoptosis of PBMCs compared with SHEDs and DPSCs. The addition of IFN-γaugmented the proliferation of DFSCs. Furthermore, the DFSCs suppressed IL-4 and IFN-γcytokine levels and enhanced IL-10 levels compared with the other cell sources.Conclusion. These results suggest that IFN-γstimulates DFSCs by inducing an immunomodulatory effect on the PBMCs of healthy donors while suppressing apoptosis and proliferation and increasing the number of CD4+FoxP3+cells.

scholarly journals Differences of Clonogenic Mesenchymal Stem Cells on Immunomodulation of Lymphocyte Subsets

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Pascual Martínez-Peinado ◽  
Sandra Pascual-García ◽  
Enrique Roche ◽  
José Miguel Sempere-Ortells
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Wide Spectrum ◽  
Fold Change ◽  
Heterogeneous Environments ◽  
Peripheral Blood Mononuclear ◽  
Proliferation Assays

Mesenchymal stem cells (MSC) are a widely used population in cell therapy for their ability to differentiate into distinct tissues and more lately, for their immunomodulatory properties. However, the use of heterogeneous populations could be responsible for the nondesired outcomes reflected in the literature. Here, we analyse the different capacities of five one-cell-derived MSC clones to exert their immunomodulation ex vivo. We assessed proliferation assays in cocultures of MSC clones and purified cluster of differentiation (CD)3+, CD4+, or CD8+ lymphocytes; analysed the regulatory T (Treg) cells fold change rate; determined the effects on viability of peripheral blood mononuclear cells (PBMC); and also measured the coculture cytokine profiles (Th1/Th2). Conditioned media (CM) of different clones were also used to perform both proliferation assays and to analyse Treg fold change. The five clones analysed in this work were able to generate heterogeneous environments. Different clones inhibited proliferation of CD3+ and CD4+ lymphocytes, with different intensities. Surprisingly, all clones promoted proliferation of CD8+ lymphocytes. Different MSC clones and their CM were able to increase the number of Treg with different intensities. Finally, different clones also promoted different effects on the viability of PBMC treated with ultraviolet light. Considering all these data together, it seems that different clones, even from the same donor, can promote a wide spectrum of responses from anti-inflammatory to proinflammatory character. This fact may be important to standardise the design of personalized cell therapy protocols, thus diminishing the aforementioned undesired outcomes existing nowadays in this type of therapies.

scholarly journals Adiponectin Isoforms and Leptin Impact on Rheumatoid Adipose Mesenchymal Stem Cells Function

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Urszula Skalska ◽  
Ewa Kontny
Keyword(s):  
Stem Cells ◽  
Molecular Weight ◽  
Mesenchymal Stem Cells ◽  
Mononuclear Cells ◽  
Secretory Activity ◽  
Synovial Fibroblasts ◽  
Infrapatellar Fat Pad ◽  
Strong Impact ◽  
Peripheral Blood Mononuclear ◽  
Adipose Mesenchymal Stem Cells

Adiponectin and leptin have recently emerged as potential risk factors in rheumatoid arthritis (RA) pathogenesis. In this study we evaluated the effects of adiponectin and leptin on immunomodulatory function of adipose mesenchymal stem cells (ASCs) derived from infrapatellar fat pad of RA patients. ASCs were stimulated with leptin, low molecular weight (LMW) and high/middle molecular weight (HMW/MMW) adiponectin isoforms. The secretory activity of ASCs and their effect on rheumatoid synovial fibroblasts (RA-FLS) and peripheral blood mononuclear cells (PBMCs) from healthy donors have been analysed. RA-ASCs secreted spontaneously TGFβ, IL-6, IL-1Ra, PGE2, IL-8, and VEGF. Secretion of all these factors was considerably upregulated by HMW/MMW adiponectin, but not by LMW adiponectin and leptin. Stimulation with HMW/MMW adiponectin partially abolished proproliferative effect of ASC-derived soluble factors on RA-FLS but did not affect IL-6 secretion in FLS cultures. ASCs pretreated with HMW/MMW adiponectin maintained their anti-inflammatory function towards PBMCs, which was manifested by moderate PBMCs proliferation inhibition and IL-10 secretion induction. We have proved that HMW/MMW adiponectin stimulates secretory potential of rheumatoid ASCs but does not exert strong impact on ASCs function towards RA-FLS and PBMCs.

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