Lung-Resident Mesenchymal Stem Cells Promote Repair of LPS-Induced Acute Lung Injury via Regulating the Balance of Regulatory T cells and Th17 cells

Wang, Linlin; Shi, Meng; Lin, Tongyu; Wang, Jian; Ji, Shimeng; Bi, Jianzhong; Chen, Cuicui; Jiang, Jinjun; Bai, Chunxue; Zhou, Ji; Song, Yuanlin

doi:10.1007/s10753-018-0884-6

Cited by 42 publications

(29 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MSCs also govern the specific types of immune cells that are recruited to sites of injury; biased towards the infiltration of tolerogenic cell types like regulatory T cells. In a recent study by Wang et al 56 , an improvement in LPS-induced ALI mediated by MSCs was dependent on the regulation of the balance between regulatory T cells and Th17 cells. Increased regulatory T cells were also observed in a mouse model of lung contusion following IV MSC administration 57 .…”

Section: Rationale For Msc Therapy To Manage Covid-19 Mediated Acute mentioning

confidence: 96%

Insights into the use of mesenchymal stem cells in COVID-19 mediated acute respiratory failure

2020

View full text Add to dashboard Cite

The emergence of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) at the end of 2019 in Hubei province China, is now the cause of a global pandemic present in over 150 countries. COVID-19 is a respiratory illness with most subjects presenting with fever, cough and shortness of breath. In a subset of patients, COVID-19 progresses to hypoxic respiratory failure and acute respiratory distress syndrome (ARDS), both of which are mediated by widespread inflammation and a dysregulated immune response. Mesenchymal stem cells (MSCs), multipotent stromal cells that mediate immunomodulation and regeneration, could be of potential benefit to a subset of COVID-19 subjects with acute respiratory failure. In this review, we discuss key features of the current COVID-19 outbreak, and the rationale for MSC-based therapy in this setting, as well as the limitations associated with this therapeutic approach.

show abstract

Section: Rationale For Msc Therapy To Manage Covid-19 Mediated Acute mentioning

confidence: 96%

Insights into the use of mesenchymal stem cells in COVID-19 mediated acute respiratory failure

2020

View full text Add to dashboard Cite

show abstract

“…When exposed to endotoxin or TNF-α, MSCs increased production of PGE 2 , which induced resident macrophage polarization toward the anti-inflammatory M2 phenotype and increased production of IL-10 (Németh et al 2009). In this context, enhanced production of IL-10 has been correlated with inhibition of rolling, adhesion, and transmigration of neutrophils (Németh et al 2009) and suppression of effector T cell neutrophil extracellular trap; NF-κB, nuclear factor-κB; o.a., oropharyngeal aspiration; PDGF, platelet-derived growth factor; TIMP, tissue inhibitor of metalloproteinase; TGF, transforming growth factor; TLR, toll-like receptor; TNF, tumor necrosis factor; TSG-6, TNF-inducible gene 6; UC, umbilical cord-derived; VEGF, vascular endothelial growth factor; VILI, ventilatorinduced lung injury proliferation (Chen et al 2014), while inducing regulatory T cell expansion (Sun et al 2011;Chao et al 2014;Wang et al 2019) and reprogramming other macrophages into the M2 phenotype (Németh et al 2009;Vasandan et al 2016). Although several studies have indicated an increase in IL-10 levels after MSC therapy, others have demonstrated a reduction in the inflammatory process with no change (Gupta et al 2012;Krasnodembskaya et al 2012) or even a decrease in IL-10 levels (Mei et al 2010;Sepúlveda et al 2014).…”

Section: Therapeutic Benefits Of Msc Therapy In Experimental Ardsmentioning

confidence: 99%

Current understanding of the therapeutic benefits of mesenchymal stem cells in acute respiratory distress syndrome

et al. 2019

View full text Add to dashboard Cite

The acute respiratory distress syndrome (ARDS) is a multifaceted lung disorder in which no specific therapeutic intervention is able to effectively improve clinical outcomes. Despite an improved understanding of molecular mechanisms and advances in supportive care strategies, ARDS remains associated with high mortality, and survivors usually face longterm morbidity. In recent years, preclinical studies have provided mounting evidence of the potential of mesenchymal stem cell (MSC)-based therapies in lung diseases and critical illnesses. In several models of ARDS, MSCs have been demonstrated to induce antiinflammatory and anti-apoptotic effects, improve epithelial and endothelial cell recovery, and enhance microbial and alveolar fluid clearance, thus resulting in improved lung and distal organ function and survival. Early-stage clinical trials have also demonstrated the safety of MSC administration in patients with ARDS, but further, large-scale investigations are required to assess the safety and efficacy profile of these therapies. In this review, we summarize the main mechanisms whereby MSCs have been shown to exert therapeutic effects in experimental ARDS. We also highlight questions that need to be further elucidated and barriers that must be overcome in order to efficiently translate MSC research into clinical practice.

show abstract

“…8). Several studies have veri ed that Treg/Th17 skewing plays a crucial role in ARDS (7,8,10,25,26). LPS, an endotoxin originating from the cell wall of gram-negative bacteria, was most used for a bacterial hyperin ammatory model of experimental ARDS (27).…”

Section: Effects Of Mir-155 Expression On Proliferation Capacity and mentioning

confidence: 99%

Mesenchymal Stem Cells-Secreted TGF-β1 Restores Treg/Th17 Skewing Induced by Lipopolysaccharide and Hypoxia Challenge via miR-155 Suppression

Xue

Zhang

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Regulatory T cells (Treg)/T helper (Th) 17 skewing plays a crucial role in development of acute respiratory distress (ARDS). Mesenchymal stem cells (MSCs)-secreted transforming growth factor (TGF)-β1 has remarkable immunomodulatory effects on CD4+T cells, being environment sensitive and remains lack of discussion in hypoxic and inflammatory condition of ARDS.Methods: Purified mice splenic CD4+ T cells were pre-coated with anti-CD3 (5ug/ml) and anti-CD28 (2ug/ml) overnight. RAW264.7 cells were added as antigen presenting cells (APCs). T cells with and without RAW264.7 cells were treated with various LPS concentrations of 0,10,100,1000ng/ml or/and at hypoxia condition of 5% O2. Based on LPS (100ng/ml) and hypoxia condition (5% O2) as stimuli, MSCs were set in direct coculture or indirect coculture methods by transwell system. Anti-TGF-β1 neutralization antibody was added to explore the role of TGF-β1 among the soluble factors secreted by MSCs; miR-155 overexpression of CD4+T cells were performed by transfection and then were added to the MSCs-CD4+T cells coculture system in hypoxic and LPS-stimulated condition. After 48 hours, cells or supernatant were collected for detection of frequency of Treg and Th17 subsets, CD4+T cells apoptosis and proliferation capacity assay by flowcytometry, secretions of INF-γ, IL-17A, IL-21, TGF-β1 and IL-10 by ELISA, levels of miR-155, Rorc, Foxp3 and Ptpn2 mRNA expression of CD4+T cells by RT-PCR.Results: MSCs could restore the skewed Treg/Th17 induced by LPS and hypoxia as compared to groups without MSCs with increased secretion of TGF-β1, IL-10 and IL-17A(P<0.05) and attenuate the increased expression of miR-155 in CD4+T cells, which was independent on cell-to-cell contact mechanism while TGF-β1 neutralization could significantly inhibit the effects of MSCs restoring the skewed Treg/Th17 and abolished its effect on miR-155 expression in CD4+T cells.Conclusions: These findings suggested miR-155 suppression of CD4+T cells mediated MSCs-secreted TGF-β1 modulating the skewed Treg/Th17 induced by LPS-hypoxia challenge, providing evidence when proposing future T lymphocyte-targeted cell therapy in ARDS.

show abstract

Lung-Resident Mesenchymal Stem Cells Promote Repair of LPS-Induced Acute Lung Injury via Regulating the Balance of Regulatory T cells and Th17 cells

Cited by 42 publications

References 32 publications

Insights into the use of mesenchymal stem cells in COVID-19 mediated acute respiratory failure

Insights into the use of mesenchymal stem cells in COVID-19 mediated acute respiratory failure

Current understanding of the therapeutic benefits of mesenchymal stem cells in acute respiratory distress syndrome

Mesenchymal Stem Cells-Secreted TGF-β1 Restores Treg/Th17 Skewing Induced by Lipopolysaccharide and Hypoxia Challenge via miR-155 Suppression

Contact Info

Product

Resources

About