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.

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 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.

Mesenchymal Stem Cells (MSC) Exhibit Antigen Presenting (APC) and Phagocytic Properties: Implicatins to Bnone Marrow Failure during Inflammation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4249-4249 ◽  
Author(s):  
Jennifer L. Chan ◽  
Jonathan S. Harrison ◽  
Nicholas M. Ponzio ◽  
Pranela Rameshwar
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Mhc Class Ii ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Peripheral Circulation ◽  
Cd4 Cells ◽  
Activated T Cells ◽  
Peripheral Blood Mononuclear ◽  
Cell Counts

Abstract Mesenchymal stem cells (MSC) mostly surround the vasculature system of bone marrow (BM). MSC have been shown to exhibit immune suppressive properties. Since MSC express MHC Class II antigen, the question is whether these cells can act as APC. To this end, we hypothesize that MSC have the ability to present non-self antigens while acting as immune modulators. These dual roles of MSC prevent exacerbated inflammatory responses in the BM, thereby preventing hematopoietic dysfunction. A ‘dampened’ immune response in BM during insults by foreign agents could cause protection of the barrier that separates BM cavity with the periphery. The phagocytic role of MSC was shown by confocal microscopy and fluoresbrite plain YG 1.0-micron microspheres. APC property was demonstrated by challenging MSC with C. albicans (pulsed MSC), followed by exposure to CD4+ cells. The latter was obtained by immunoselection from peripheral blood mononuclear cells (PBMC) cultured for 5 days with C. albicans (10 mg/ml). Proliferation of the CD4+ cells (3H-thymidine incorporation and cell counts) proved APC properties of MSC, at efficiency comparable to macrophages. Overall, the studies show that the window between APC function and the period at which MSC could become immune suppressive is critical, since activated T-cells could destroy the endothelial barrier between BM and lymphatics/peripheral circulation. These studies show that MSC could be key cells in regulating immune responses in BM, and thereby protect BM from failure.

scholarly journals Up-regulation of CD200/CD200R1 Immunomodulatory Axis of Allogenic Peripheral Blood Mononuclear Cells in a Co-culture with Adipose-derived Mesenchymal Stem Cells

2020 ◽  
Author(s):  
Nishtman Heidari ◽  
Mobin Mohammadi ◽  
Mohammad Ali Rezaee ◽  
Abbas Ali Amini ◽  
Shohreh Fakhari ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cytotoxic T Lymphocyte ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Co-inhibitory molecules modulate immune responses. Immunomodulatory properties of mesenchymal stem cells (MSCs) turn them into ideal candidates for cell therapy. This study was designed to investigate the immunomodulatory effect of adipose-derived stem cells (ASCs) on inflammatory environment of a co-culture of allogenic peripheral blood mononuclear cells (PBMCs) in a two-way mixed leukocyte reaction (twMLR) setting. ASCs were co-cultured with allogenic PBMCs in twMLR setting for four days. The proliferation of peripheral blood mononuclear cells (PBMCs), levels of interleukin (IL)-10, and expression of interferon-gamma (IFN-γ), B7-1, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death-ligand 1 (PD-L1), +, and CD200R1 genes, as well as cell surface expression of CD200 and CD200R1, were measured in twMLR as control, and co-culture groups on days 0, 2 and 4 of the experiment. The proliferation of PBMCs was suppressed on days 2 and 4 of co-culture. The expression  of CD200 (p=0.014), CD200R1, CTLA-4, and PD1 genes increased on days 2 and 4 of the co-culture compared to twMLR. CD200 expressing PBMCs decreased by 1.75% on day 2 of the co-culture but increased by 6.23% on day 4 of the co-culture (p=0.013) compared to the same days of  twMLR. IL-10 levels increased in the co-culture supernatants on days 2 and 4 compared to twMLR (p<0.05). Our results showed that ASCs upregulate the CD200/CD200R1 axis more than PD-1/PD-L1 and CTLA-4/B7-1 pathways in the twMLR. Also, elevated expression of CD200R1 in the final day of co-culture was similar to PD-1 expression pattern. This finding suggests a role for the CD200/CD200R1 axis in later modulation of the immune response.  

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.

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