scholarly journals Depletion of ID3 enhances mesenchymal stem cells therapy by targeting BMP4 in Sjögren’s syndrome

2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Lei Hu ◽  
Junji Xu ◽  
Tingting Wu ◽  
Zhipeng Fan ◽  
Lingyun Sun ◽  
...  
2021 ◽  
Author(s):  
Yan Liu ◽  
Yi Xiong Chen ◽  
Nancy Olsen ◽  
Wael Jarjour ◽  
Yan Lu ◽  
...  

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.


2019 ◽  
Vol 20 (19) ◽  
pp. 4750 ◽  
Author(s):  
Ghada Abughanam ◽  
Osama A. Elkashty ◽  
Younan Liu ◽  
Mohammed O. Bakkar ◽  
Simon D. Tran

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.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Weiqian Chen ◽  
Ye Yu ◽  
Jilin Ma ◽  
Nancy Olsen ◽  
Jin Lin

Primary Sjögren’s syndrome (pSS) is a chronic systemic inflammatory autoimmune disease characterized by lymphocytic infiltrates in exocrine glands. Current approaches do not control harmful autoimmune attacks or prevent irreversible damage and have considerable side effects. Mesenchymal stem cells (MSCs) have been effective in the treatment of several autoimmune diseases. The objective of this review is to illustrate the potential therapeutic role of MSCs in pSS. We summarize the recent advances in what is known about their immunomodulatory function and therapeutic applications in pSS. MSC transfusion can suppress autoimmunity and restore salivary gland secretory function in mouse models and patients with pSS by inducing regulatory T cells, suppressing Th1, Th17, and T follicular helper cell responses. In addition, MSCs can differentiate into salivary epithelial cells, presenting an option as a suitable alternative treatment. We also discuss current bioengineering methods which improve functions of MSCs for pSS. However, there remain many challenges to overcome before their wide clinical application.


2021 ◽  
Vol 22 (19) ◽  
pp. 10474
Author(s):  
Najwa Chihaby ◽  
Marie Orliaguet ◽  
Laëtitia Le Pottier ◽  
Jacques-Olivier Pers ◽  
Sylvie Boisramé

Mesenchymal stem cells (MSCs) are ubiquitous in the human body. Mesenchymal stem cells were initially isolated from bone marrow and later from other organs such as fatty tissues, umbilical cords, and gingiva. Their secretory capacities give them interesting immunomodulatory properties in cell therapy. Some studies have explored the use of MSCs to treat Sjögren’s syndrome (SS), a chronic inflammatory autoimmune disease that mainly affects exocrine glands, including salivary and lacrimal glands, although current treatments are only palliative. This systematic review summarizes the current data about the application of MSCs in SS. Reports show improvements in salivary secretions and a decrease in lymphocytic infiltration in salivary glands in patients and mice with SS after intravenous or infra-peritoneal injections of MSCs. MSC injections led to a decrease in inflammatory cytokines and an increase in anti-inflammatory cytokines. However, the intrinsic mechanism of action of these MSCs currently remains unknown.


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