BMSC-derived exosomes alleviate smoke inhalation lung injury through blockade of the HMGB1/NF-κB pathway

Xu, Baojun; Gan, Chunxia; Chen, Sisi; Li, Jiaqi; Liu, Mingzhuo; Guo, Guang-hua

doi:10.1016/j.lfs.2020.118042

Cited by 29 publications

(19 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…EVs are regarded as significant signalling mediators for intercellular communication, partially due to their ability to transport particular proteins, mRNA, and microRNA (Camussi et al., 2010 ). Multiple preclinical studies supported MSC‐EVs to be a potential therapeutic strategy for ALI caused by different types of non‐infectious factors, such as LPS (Kaspi et al., 2021 ), smoke inhalation (Xu et al., 2020 ), burn (Liu et al., 2019 ) and trauma (Li et al., 2019 ). Besides, there is also a large body of evidence demonstrating that lung inflammation resulting from tracheal inoculation of live Escherichia coli (Curley et al., 2017 ; Devaney et al., 2015 ; Gupta et al., 2012 ; Kim et al., 2011 ; Lee et al., 2013 ; Monsel et al., 2015 ; Park et al., 2019 ; Sung et al., 2016 ) and Pseudomonas aeruginosa (PA) (Mao et al., 2015 ) is significantly reduced by MSCs (Curley et al., 2017 ; Devaney et al., 2015 ; Gupta et al., 2012 ; Kim et al., 2011 ; Lee et al., 2013 ; Mao et al., 2015 ; Sung et al., 2016 ) and MSC‐EVs (Monsel et al., 2015 ; Park et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Preclinical efficacy and clinical safety of clinical‐grade nebulized allogenic adipose mesenchymal stromal cells‐derived extracellular vesicles

Shi

Yang

Monsel

et al. 2021

J of Extracellular Vesicle

103

View full text Add to dashboard Cite

Mesenchymal stromal cell‐derived extracellular vesicles (MSC‐EVs) turn out to be a promising source of cell‐free therapy. Here, we investigated the biodistribution and effect of nebulized human adipose‐derived MSC‐EVs (haMSC‐EVs) in the preclinical lung injury model and explored the safety of nebulized haMSC‐EVs in healthy volunteers. DiR‐labelled haMSC‐EVs were used to explore the distribution of nebulized haMSC‐EVs in the murine model. Pseudomonas aeruginosa‐induced murine lung injury model was established, and survival rate, as well as WBC counts, histology, IL‐6, TNF‐α and IL‐10 levels in bronchoalveolar lavage fluid (BALF) were measured to explore the optimal therapeutic dose of haMSC‐EVs through the nebulized route. Twenty‐four healthy volunteers were involved and received the haMSC‐EVs once, ranging from 2 × 108 particles to 16 × 108 particles (MEXVT study, NCT04313647). Nebulizing haMSC‐EVs improved survival rate to 80% at 96 h in P. aeruginosa‐induced murine lung injury model by decreasing lung inflammation and histological severity. All volunteers tolerated the haMSC‐EVs nebulization well, and no serious adverse events were observed from starting nebulization to the 7th day after nebulization. These findings suggest that nebulized haMSC‐EVs could be a promising therapeutic strategy, offering preliminary evidence to promote the future clinical applications of nebulized haMSC‐EVs in lung injury diseases.

show abstract

Section: Introductionmentioning

confidence: 99%

Preclinical efficacy and clinical safety of clinical‐grade nebulized allogenic adipose mesenchymal stromal cells‐derived extracellular vesicles

Shi

Yang

Monsel

et al. 2021

J of Extracellular Vesicle

103

View full text Add to dashboard Cite

show abstract

“…Diverse regulatory mechanisms, including the NF- κ B [ 16 ] and mitogen-activated protein kinase (MAPK) cascades [ 17 ], are known to participate in the multidirectional differentiation of MSCs. In 1986, the A B cell-specific inducible transcription factor was discovered by the research group of David Baltimore and identified as nuclear factor- κ B (NF- κ B) [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

iRoot SP Promotes Osteo/Odontogenesis of Bone Marrow Mesenchymal Stem Cells via Activation of NF-κB and MAPK Signaling Pathways

Yan

et al. 2020

Stem Cells International

View full text Add to dashboard Cite

The regeneration of bone and tooth tissues, and related cellular therapies, has attracted widespread attention. Bone marrow mesenchymal stem cells (BMSCs) are potential candidates for such regeneration. iRoot SP is a premixed bioceramic root canal sealer widely used in clinical settings. However, the effect of iRoot SP on the biological features of BMSCs has not been elucidated. In the present study, we found that 0.2 mg/ml iRoot SP conditioned medium promoted osteo/odontogenic differentiation and enhanced mineralization of BMSCs without affecting the proliferative ability. Mechanistically, the NF-κB and MAPK signaling pathways were activated in SP-treated BMSCs, and differentiation was inhibited when cultured with the specific inhibitor. Taken together, these findings demonstrate that iRoot SP promotes osteo/odontogenic differentiation of BMSCs via the NF-κB and MAPK signaling pathways, which could provide a new theoretical basis for clinical applications of iRoot SP and a new therapeutic target for the regeneration of bone and tooth tissue in the future.

show abstract

“…43 EVs derived from MSCs could downregulate the expression of proinflammatory cytokines IL-1β and IL-6 in epithelial cells of cystic fibrosis. 44 Xu et al 45 reported that bone marrow mesenchymal stem cells (BMSCs)-derived exosomes can effectively rescue smoke inhalation lung injury by inhibiting the HMGB1/NF-κB pathway, suggesting the potential therapeutic role of EVs in treating smoke inhalation lung injury. Moreover, a recent study by Ridzuan et al 46 revealed that human umbilical cord mesenchymal stem cells (HUCMSCs) derived-EVs reduced the COPD-induced inflammation in part by the expression of NF-κB subunits p65 and p50.…”

Section: Discussionmentioning

confidence: 99%

Endothelial Microparticles Derived from Primary Pulmonary Microvascular Endothelial Cells Mediate Lung Inflammation in Chronic Obstructive Pulmonary Disease by Transferring microRNA-126

Liu

Long

et al. 2022

JIR

View full text Add to dashboard Cite

Background: Extracellular vesicles (EVs) are considered to new types of intercellular communication media, and microRNA is one of the most common transferring components of EVs. This study aimed to explore the potential role of endothelial microparticles (EMPs) derived from primary pulmonary microvascular endothelial cells in regulating lung inflammation of chronic obstructive pulmonary disease (COPD) through transferring microRNA-126 (miR-126). Methods: EMPs generated from primary pulmonary microvascular endothelial cells were isolated by gradient centrifugation and characterized by transmission electron microscopy, flow cytometry and Western blotting. EMPs were treated to in vitro and in vivo COPD models induced by cigarette smoke extract (CSE). miR-126 mimics or inhibitors were transfected into EMPs by calcium chloride. Pathological changes of lung tissue, mRNA and protein levels of inflammation-related factors were measured to explore the effect of EMPs transferring miR-126 on CSE-induced inflammation. Results: Both in vitro and in vivo studies demonstrated that mRNA and protein levels of inflammation-related factors were significantly increased in COPD group, while EMPs could dramatically reverse these increases. In vitro, overexpression of miR-126 in EMPs decreased HMGB1 expression and magnified the decreasing effect of EMPs on inflammation-related factors. Conclusion:The present study reveals that EMPs are capable of alleviating lung inflammation and transferring miR-126 can magnify the anti-inflammatory effect of EMPs, which may provide a novel therapeutic alternative for COPD.

show abstract

BMSC-derived exosomes alleviate smoke inhalation lung injury through blockade of the HMGB1/NF-κB pathway

Cited by 29 publications

References 61 publications

Preclinical efficacy and clinical safety of clinical‐grade nebulized allogenic adipose mesenchymal stromal cells‐derived extracellular vesicles

Preclinical efficacy and clinical safety of clinical‐grade nebulized allogenic adipose mesenchymal stromal cells‐derived extracellular vesicles

iRoot SP Promotes Osteo/Odontogenesis of Bone Marrow Mesenchymal Stem Cells via Activation of NF-κB and MAPK Signaling Pathways

Endothelial Microparticles Derived from Primary Pulmonary Microvascular Endothelial Cells Mediate Lung Inflammation in Chronic Obstructive Pulmonary Disease by Transferring microRNA-126

Contact Info

Product

Resources

About