Human umbilical cord mesenchymal stem cells confer potent immunosuppressive effects in Sjögren’s syndrome by inducing regulatory T cells

2020 ◽  
Vol 31 (1) ◽  
pp. 186-196 ◽  
Author(s):  
Yanying Liu ◽  
Chunlei Li ◽  
Shiyao Wang ◽  
Jing Guo ◽  
Jianping Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory T Cells ◽  
Umbilical Cord ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Human Umbilical Cord ◽  
Sjögren‘S Syndrome

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 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.

scholarly journals T Cells Subsets in the Immunopathology and Treatment of Sjogren’s Syndrome

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1539
Author(s):  
William de Jesús Ríos-Ríos ◽  
Sorely Adelina Sosa-Luis ◽  
Honorio Torres-Aguilar
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Disease Progression ◽  
Sjögren’S Syndrome ◽  
Cd8 T Cells ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren‘S Syndrome

Sjogren’s syndrome (SS) is an autoimmune disease whose pathogenesis is characterized by an exacerbated T cell infiltration in exocrine glands, markedly associated to the inflammatory and detrimental features as well as the disease progression. Several helper T cell subsets sequentially converge at different stages of the ailment, becoming involved in specific pathologic roles. Initially, their activated phenotype endows them with high migratory properties and increased pro-inflammatory cytokine secretion in target tissues. Later, the accumulation of immunomodulatory T cells-derived factors, such as IL-17, IFN-γ, or IL-21, preserve the inflammatory environment. These effects favor strong B cell activation, instigating an extrafollicular antibody response in ectopic lymphoid structures mediated by T follicular helper cells (Tfh) and leading to disease progression. Additionally, the memory effector phenotype of CD8+ T cells present in SS patients suggests that the presence of auto-antigen restricted CD8+ T cells might trigger time-dependent and specific immune responses. Regarding the protective roles of traditional regulatory T cells (Treg), uncertain evidence shows decrease or invariable numbers of circulating and infiltrating cells. Nevertheless, an emerging Treg subset named follicular regulatory T cells (Tfr) seems to play a critical protective role owing to their deficiency that enhances SS development. In this review, the authors summarize the current knowledge of T cells subsets contribution to the SS immunopathology, focusing on the cellular and biomolecular properties allowing them to infiltrate and to harm target tissues, and that simultaneously make them key therapeutic targets for SS treatment.

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