scholarly journals Mesenchymal Stem Cells Activate the MEK/ERK Signaling Pathway and Enhance DNA Methylation via DNMT1 in PBMC from Systemic Lupus Erythematosus

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Hui Xiong ◽  
Zhixuan Guo ◽  
Zengqi Tang ◽  
Xuechen Ai ◽  
Qing Qi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dna Methylation ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathway ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Erk Signaling ◽  
Control Group ◽  
Systemic Lupus

The defective MEK/ERK signaling pathway and downstream hypomethylation pattern of lymphocytes are crucial for the pathogenesis of systemic lupus erythematosus (SLE). However, the role that the mesenchymal stem cells play in the MEK/ERK signaling pathway and DNA methylation of peripheral blood mononuclear cells (PBMC) from SLE patients remains unknown. In this study, we found that the MEK/ERK signaling pathway of PBMC from SLE patients was activated after the coculture with bone marrow-derived mesenchymal stem cells (BM-MSC) compared with that from the control group. In addition, the expression level of DNA methyltransferase 1 (DNMT1) increased while the levels of CD70, integrin, alpha L (ITGAL), selectin-l, and IL-13 were reduced in PBMC from SLE patients. However, no obvious effect of BM-MSC on PBMC from healthy controls was observed. These findings revealed that BM-MSC might downregulate the expression of methylation-sensitive genes and then suppress the autoactivated PBMC via the MEK/ERK signaling pathway. And it may be one of the mechanisms that BM-MSC ameliorated SLE.

scholarly journals The Role of Mesenchymal Stem Cells in Decreasing Interleukin-12 Human Systemic Lupus Erythematosus

2020 ◽  
Vol 8 (A) ◽  
pp. 787-792
Author(s):  
Delfitri Munir ◽  
Rodiah Rahmawaty Lubis ◽  
Dewi Masyithah Darlan ◽  
Agung Putra ◽  
Iffan Allif
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Interleukin 12 ◽  
Control Group ◽  
Systemic Lupus ◽  
Control Group Design

BACKGROUND: Systemic lupus erythematosus (SLE) disease is characterized by a loss of self-tolerance leading to a local tissue inflammation up to a massive systemic organ-spesific inflammation. Mesenchymal stem cells (MSCs) present immunomodulatory properties to control the over-activating immune responses in SLE through several mechanisms. However, the capability of MSCs to decrease interleukin (IL)-12 production in in vitro remains unclear. AIM: The aim of this study was to investigate the role of MSCs in decreasing the level of IL-12 derived from peripheral blood mononuclear cells (PBMCs) of SLE patients. METHODS: This study used a post-test control group design using a coculture of PBMCs from SLE and healthy patients with MSCs as the subjects. This study included five groups: sham (Sh), control (C), and treatment groups (T) treated by a co-culture MSCs with PBMCs at ratio dose of 1:1 (T1), 1:25 (T2), and 1:50 (T3), respectively, for 72 hours of incubation. The IL-12 levels was analysed by cytometric bead array (CBA) of flow cytometry. RESULTS: This study showed a significant decrease of IL-12 levels (p < 0.05) in T1 and T2 after 72 hours incubation of co-culture MSCs with PBMCs from SLE patient. CONCLUSION: MSCs could decrease the level of IL-12 in PBMCs of human SLE to control the inflammation of SLE disease.

Toll-like receptor signalling associated with immunomodulation of umbilical cord–derived mesenchymal stem cells in mice with systemic lupus erythematosus

Lupus ◽  
2020 ◽  
Vol 29 (2) ◽  
pp. 165-175
Author(s):  
K H Wu ◽  
C C Cheng ◽  
J P Li ◽  
T F Weng ◽  
S F Yang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Lupus Erythematosus ◽  
Quantitative Polymerase Chain Reaction ◽  
Control Group ◽  
Toll Like Receptor ◽  
Systemic Lupus ◽  
Altered Expression ◽  
Receptor Signalling

With potent immunomodulatory activities, mesenchymal stem cells (MSCs) have the potential to be a beneficial treatment option for diseases with aberrant immune responses such as systemic lupus erythematosus (SLE). However, the underlying mechanisms remain largely unknown. Here, we used NZBWF1 mice as a SLE animal model to examine immunomodulation of MSCs as well as to assess the role of Toll-like receptor signalling in this circumstance. We found that mice receiving MSCs had a significant decrease in severity of proteinuria at 20 and 22 weeks of age ( p = 0.009 and p = 0.022, respectively). Serum anti-dsDNA levels were significantly lower compared with the control group ( p = 0.016 and p = 0.036, respectively). C3 and C4 levels were significantly higher at 22 weeks of age ( p = 0.046 and p = 0.016, respectively). Altered expression of inflammation-associated cytokine profiles in the serum was also noted in mice receiving MSCs. Down-regulation of myeloid differentiation factor 88 (MyD88)-nuclear factor-κB (NF-κB) signalling in the liver was demonstrated by quantitative polymerase chain reaction, ELISA and Western blotting. In addition to demonstrating the beneficial effects of MSC treatment in NZBWF1 mice, our study provided the first evidence for the association of MyD88-NF-κB signalling and MSC-mediated immunomodulation in this disease.

scholarly journals Clinical Efficacy and Safety of Mesenchymal Stem Cells for Systemic Lupus Erythematosus

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Tianbiao Zhou ◽  
Hong-Yan Li ◽  
Chunling Liao ◽  
Wenshan Lin ◽  
Shujun Lin
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adverse Events ◽  
Lupus Erythematosus ◽  
Meta Analysis ◽  
Case Series ◽  
Control Group ◽  
Efficacy And Safety ◽  
Systemic Lupus

Systemic lupus erythematosus (SLE) is a polymorphic, multisystemic autoimmune disease that causes multiorgan damage in which cellular communication occurs through the involvement of autoantibodies directed against autoantigen production. Mesenchymal stem cells (MSCs), which have strong protective and immunomodulatory abilities, are obtained not only from bone marrow but also from medical waste such as adipose tissue and umbilical cord tissue and have been recognized as a promising tool for the treatment of various autoimmune diseases and inflammatory disorders. This meta-analysis is aimed at assessing whether MSCs can become a new treatment for SLE with good efficacy and safety. Based on predetermined criteria, a bibliographical search was performed from January 1, 2000, to July 31, 2019, by searching the following databases: ISI Web of Science, Embase, PubMed, the Cochrane Library, and the Chinese Biomedical Literature Database (CBM). Eligible studies and data were identified. Statistical analysis was conducted to assess the efficacy (proteinuria, systemic lupus erythematosus disease activity index (SLEDAI), Scr, BUN, albumin, C3, and C4) and safety (rate of adverse events) of MSCs for SLE using Cochrane Review Manager Version 5.3. Ten studies fulfilled the inclusion criteria and were eligible for this meta-analysis, which comprised 8 prospective or retrospective case series and four randomized controlled trails (RCTs) studies. In the RCT, the results indicated that the MSC group had lower proteinuria than the control group at 3 months and 6 months and the MSC group displayed a lower SLEDAI than the control group at 2 months and 6 months. Furthermore, the MSC group showed a lower rate of adverse events than the control group (OR=0.26, 95% CI: 0.07, 0.89, P=0.03). In the case series trials, the results indicated that the MSC group had lower proteinuria at 1 month, 2 months, 3 months, 4 months, 6 months, and 12 months. In conclusion, MSCs might be a promising therapeutic agent for patients with SLE.

Stem cell transplantation: progress in Asia

Lupus ◽  
2010 ◽  
Vol 19 (12) ◽  
pp. 1468-1473 ◽  
Author(s):  
L. Sun
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Hematopoietic Stem ◽  
The Past ◽  
Complex Autoimmune Disease ◽  
Significant Mortality

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multiorgan involvement and high mortality, which was reduced because of the most widely and classically used immunosuppressive therapies. However, some patients continue to have significant mortality. So a shift in the approach to the treatment of SLE is needed. In the past decade, most transplants have been performed in the treatment of SLE with allogeneic or autologous hematopoietic stem cells and currently emerging mesenchymal stem cells. There are some important differences between the two procedures.

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