SAT0187 Immunomodulatory effects of human umbilical cord wharton jelly-derived mesenchymal stem cells (HUCMS) on circulating T-cell subsets in patients with sjögren’s syndrome

2013 ◽  
Vol 71 (Suppl 3) ◽  
pp. 534.3-535
Author(s):  
A. Alunno ◽  
P. Montanucci ◽  
O. Bistoni ◽  
G. Basta ◽  
S. Caterbi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Umbilical Cord ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
T Cell Subsets ◽  
Human Umbilical Cord ◽  
Immunomodulatory Effects ◽  
Sjögren‘S Syndrome

scholarly journals Bone Morphogenetic Protein 6 Inhibits the Immunomodulatory Property of BMMSCs via Id1 in Sjögren’s Syndrome

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Yingying Su ◽  
Yi Gu ◽  
Ruiqing Wu ◽  
Hao Wang
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
T Cell Proliferation ◽  
Sjögren‘S Syndrome

Mesenchymal stem cells (MSCs) treatment has emerged as a promising approach for treating Sjögren’s syndrome (SS). Impaired immunoregulatory activities of bone marrow mesenchymal stem cells (BMMSCs) are found in both SS patients and animal models, and the underlying mechanism is poorly understood. Increased expression of BMP6 is reported to be related to SS. The aim herein was to determine the effects of BMP6 on BMMSCs function. BMMSCs were isolated from SS patients and NOD mice and showed a high level of BMP6 expression. The effects of BMP6 on BMMSCs function were investigated using in vitro BMMSCs differentiation and in vitro and in vivo T cell proliferation and polarization assays. BMP6 increased osteogenic differentiation of BMMSCs and inhibited the immunomodulatory properties of BMMSCs. BMP6 enhanced T cell proliferation and Th1/Th17 differentiation in a T cell-BMMSC coculture system. Mechanistically, BMP6 downregulated PGE2 and upregulated IFN-gamma via Id1 (inhibitor of DNA-binding protein 1). Neutralizing BMP6 and knockdown of Id1 could restore the BMMSCs immunosuppressive function both in vitro and in vivo. The present results suggest a novel role of Id1 in BMP-mediated MSCs function, which may contribute to a better understanding of the mechanism of action of MSCs in treating autoimmune diseases.

Therapeutic Effect of Mesenchymal Stem Cells on Sjögren's Syndrome: Systematic Review and a Preclinical Meta-Analysis

2021 ◽  
Author(s):  
Yan Liu ◽  
Yi Xiong Chen ◽  
Nancy Olsen ◽  
Wael Jarjour ◽  
Yan Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Meta Analysis ◽  
Treatment Strategies ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Therapeutic Effects ◽  
Sjögren‘S Syndrome

Abstract BackgroundEvidence to support Mesenchymal stem cells (MSCs) treatment in Sjögren's syndrome (SS) has been verified. This study aims to evaluate the effectiveness of heterogeneous MSCs therapies, identify optimal experimental parameters and explore possible underlying mechanisms in animal models of SS.MethodsLiterature searches were performed in PubMed, Web of Science and EMBASE. Effect sizes of SS treatments with MSCs were extracted and analyzed by two authors independently.ResultsA total of 13 studies and 20 treatment arms met the inclusion criteria. When compared with the controls, MSCs treatment resulted in lower level of histological score (SMD= -2.208; 95%CI= -3.129, -1.286; P<0.001) accompanied by an improved trend of salivary flow rate (SFR) (SMD = 1.726; 95%CI= 1.340, 2.113; P <0.001) and Schirmer's test results (SMD= 3.379; 95% CI= 2.141, 4.618; P<0.001). In MSCs groups, levels of autoantibodies decreased to varying degrees. Treg cells were increased and Th17 cells were decreased in both lymph nodes and spleens. Additionally, IL-6 reduction and IL-10 elevation were found in local lesional tissues. Furthermore, TNF-α level dropped either in sera or glands. Notably, the cell injection frequency and routes may be two important factors affecting the effect of MSCs therapy.ConclusionTo the best of our knowledge, this is the first meta-analysis to quantitatively evaluate MSCs therapeutic effects on SS. Our research emphasizes optimizing MSC treatment strategies to achieve better outcomes, thereby providing a valuable reference for clinical application.

scholarly journals Human Umbilical Cord Mesenchymal Stem Cells Inhibit the Function of Allogeneic Activated Vγ9Vδ2 T Lymphocytes In Vitro

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaohuan Liu ◽  
Ting Feng ◽  
Tianxiang Gong ◽  
Chongyang Shen ◽  
Tingting Zhu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Umbilical Cord ◽  
Interleukin 2 ◽  
Cell Contact ◽  
Human Umbilical Cord ◽  
Fas L

Background. Human umbilical cord mesenchymal stem cells (UC-MSCs) can regulate the function of immune cells. However, whether and how UC-MSCs can modulate the function of Vγ9Vδ2 T cells has not been fully understood. Methods. The PBMCs or Vγ9Vδ2 T cells were activated and expanded with pamidronate (PAM) and interleukin-2 (IL-2) with or without the presence UC-MSCs. The effects of UC-MSCs on the proliferation, cytokine expression, and cytotoxicity of Vγ9Vδ2 T cells were determined by flow cytometry. The effects of UC-MSCs on Fas-L, TRAIL-expressing Vγ9Vδ2 T cells, and Vγ9Vδ2 T cell apoptosis were determined by flow cytometry. Results. UC-MSCs inhibited Vγ9Vδ2 T cell proliferation in a dose-dependent but cell-contact independent manner. Coculture with UC-MSCs reduced the frequency of IFNγ+ but increased granzyme B+ Vγ9Vδ2 T cells. UC-MSCs inhibited the cytotoxicity of Vγ9Vδ2 T cells against influenza virus H1N1 infected A549 cells and also reduced the frequency of Fas-L+, TRAIL+ Vγ9Vδ2 T cells but failed to modulate the apoptosis of Vγ9Vδ2 T cells. Conclusions. These results indicated that UC-MSCs efficiently suppressed the proliferation and cytotoxicity of Vγ9Vδ2 T cells and modulated their cytokine production. Fas-L and TRAIL were involved in the regulation. Cell contact and apoptosis of Vγ9Vδ2 T cells were not necessary for the inhibition.

Comparative Study of the Biological Characteristics of Serum-Free and Fetal Bovine Serum-Contained Medium Cultured Umbilical Cord-Derived Mesenchymal Stem Cells

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4737-4737 ◽  
Author(s):  
Guanghua Chen ◽  
Ting Yang ◽  
Man Qiao ◽  
Huiwen Liu ◽  
Wu Depei
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Umbilical Cord ◽  
Complete Medium ◽  
Human Umbilical Cord ◽  
Serum Free Medium ◽  
Free Medium ◽  
Early Passage ◽  
Serum Free

Abstract Abstract 4737 Objective: To compare the difference of biological characteristics between human umbilical cord-derived mesenchymal stem cells (UC-MSC) cultured by serum free medium and fetal bovine serum-contained complete medium and to create a xenogeneic protein-free UC-MSC culture system. Methods: Healthy human umbilical cord segments were digested with collagenase. Umbilical cord-derived mesenchymal stem cells were cultured by serum free MesenCult-XF medium and FBS-based αMEM complete medium. We analysed the morphology, immunophenotype, expansion potential, trilineage differentiation potential, karyotype and immunosuppression of early passage of UC-MSC. Results: The average cell diameters of UC-MSC in suspension cultured by serum free medium and FBS-based medium are 26 (18–39) μm and 35 (20–61) μm, respectively. Cell expansion folds with serum free medium and FBS-based medium were (5.2±0.2) and (3.5±0.1) in the first five passage, respectively. The expansion potential of MSCs was significantly higher with serum free medium compared to FBS-based medium (P<0.05). A panel of markers as CD29, CD44, CD90, CD73, CD105 and HLA-ABC were expressed by human UC-MSC. Hematopoietic lineage markers CD34, CD45 and HLA-DR were not detectable on UC-MSC. The cpm were (4.57±0.14)×104, (2.04±0.16)×104 and(0.42±0.04)×104 when serum free medium cultured MSCs were added to the cultures at ratios MSCs/T cell of 1:100, 1:10 and 1:5. While the cpm were (4.57±0.14)×104, (2.04±0.16)×104 and(0.42±0.04)×104when serum free medium cultured UC-MSCs were added to the cultures. The immunosuppressive potential of serum free medium-cultured UC-MSC was higher than that of serum-contained medium cultured UC-MSC at three different ratios MSC/T cell (P<0.05). Conclusion Compare with serum-contained medium cultured early passage of UC-MSC, the cell diameter of serum free medium cultured MSCs was smaller and the expansion potential was higher. No xenogeneic proteins were presented in UC-MSC preparation when UC-MSC was cultured with serum free medium. Human UC-MSC suppresses T-cell proliferation in a dose-dependent manner. The immunosuppressive potential of UC-MSC was higher when cultured in serum free medium compared with FBS-based medium. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Mesenchymal Stem Cells Extract (MSCsE)-Based Therapy Alleviates Xerostomia and Keratoconjunctivitis Sicca in Sjogren’s Syndrome-Like Disease

2019 ◽  
Vol 20 (19) ◽  
pp. 4750 ◽  
Author(s):  
Ghada Abughanam ◽  
Osama A. Elkashty ◽  
Younan Liu ◽  
Mohammed O. Bakkar ◽  
Simon D. Tran
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Nod Mice ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Peripheral Tolerance ◽  
Lacrimal Glands ◽  
Sjögren‘S Syndrome

Sjogren’s syndrome (SS) is an autoimmune disease that manifests primarily in salivary and lacrimal glands leading to dry mouth and eyes. Unfortunately, there is no cure for SS due to its complex etiopathogenesis. Mesenchymal stem cells (MSCs) were successfully tested for SS, but some risks and limitations remained for their clinical use. This study combined cell- and biologic-based therapies by utilizing the MSCs extract (MSCsE) to treat SS-like disease in NOD mice. We found that MSCsE and MSCs therapies were successful and comparable in preserving salivary and lacrimal glands function in NOD mice when compared to control group. Cells positive for AQP5, AQP4, α-SMA, CK5, and c-Kit were preserved. Gene expression of AQP5, EGF, FGF2, BMP7, LYZ1 and IL-10 were upregulated, and downregulated for TNF-α, TGF-β1, MMP2, CASP3, and IL-1β. The proliferation rate of the glands and serum levels of EGF were also higher. Cornea integrity and epithelial thickness were maintained due to tear flow rate preservation. Peripheral tolerance was re-established, as indicated by lower lymphocytic infiltration and anti-SS-A antibodies, less BAFF secretion, higher serum IL-10 levels and FoxP3+ Treg cells, and selective inhibition of B220+ B cells. These promising results opened new venues for a safer and more convenient combined biologic- and cell-based therapy.

Immunomodulatory effects of adipose-derived mesenchymal stem cells on the gene expression of major transcription factors of T cell subsets

2014 ◽  
Vol 20 (2) ◽  
pp. 316-321 ◽  
Author(s):  
Adel Mohammadzadeh ◽  
Ali Akbar Pourfathollah ◽  
Somayeh Shahrokhi ◽  
Seyed Mahmoud Hashemi ◽  
Sadegh Lotf Alah Moradi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transcription Factors ◽  
T Cell ◽  
T Cell Subsets ◽  
Immunomodulatory Effects
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