Mesenchymal stem cell exosomes reverse acute lung injury through Nrf-2/ARE and NF- κ B signaling pathways

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Abstract

Acute lung injury (ALI) is associated with histopathological diffuse alveolar damage. The potential role of mesenchymal stem cells (MSCs) in the treatment of various clinical disorders have been widely documented, such as those for ALI. Recent evidence has demonstrated that exosomes from endothelial progenitor cells can improve outcomes of the lipopolysaccharide (LPS)-induced ALI. However, there has been no research on the potential role of MSC-exosomes in the treatment of sepsis-induced ALI, which is worth further exploration. Thus, the objective of our study was to identify whether the MSC-exosomes could reverse ALI. The ALI model induced by LPS was established in this study. MTT assay was performed to test cell proliferation. Expression of inflammatory factors (TNF-α, IL-6, and IL-10) in the LPS-treated type II alveolar epithelial cells (AECs) (MLE-12) was detected by ELISA. After co-culture of MSC-exosomes with LPS-treated MLE-12 cells, we found that the cell proliferation of MLE-12 cells gradually increased. Furthermore, we selected five of the Nrf-2/ARE- and NF-κB signaling pathway-related genes to explore if MSC-exosomes could reverse LPS-induced ALI through Nrf-2/ARE and NF-κB signaling pathways. QRT-PCR and western blot experiment results showed that the expression of these five genes were significantly regulated after stimulation with high-concentration LPS and exosome intervention. Taken together, these findings highlighted the fact that MSC-exosomes could reverse ALI through the Nrf-2/ARE and NF-κB signaling pathways. The MSC-exosome may be the potential future therapeutic strategy for the treatment of ALI.

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Mesenchymal stem cells.

Shinn-Zong Lin, Dah-Ching Ding, Woei-Cherng Shyu (2010)

Stem cells have two features: the ability to differentiate along different lineages and the ability of self-renewal. Two major types of stem cells have been described, namely, embryonic stem cells and adult stem cells. Embryonic stem cells (ESC) are obtained from the inner cell mass of the blastocyst and are associated with tumorigenesis, and the use of human ESCs involves ethical and legal considerations. The use of adult mesenchymal stem cells is less problematic with regard to these issues. Mesenchymal stem cells (MSCs) are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as umbilical cord, endometrial polyps, menses blood, bone marrow, adipose tissue, etc. This is because the ease of harvest and quantity obtained make these sources most practical for experimental and possible clinical applications. Recently, MSCs have been found in new sources, such as menstrual blood and endometrium. There are likely more sources of MSCs waiting to be discovered, and MSCs may be a good candidate for future experimental or clinical applications. One of the major challenges is to elucidate the mechanisms of differentiation, mobilization, and homing of MSCs, which are highly complex. The multipotent properties of MSCs make them an attractive choice for possible development of clinical applications. Future studies should explore the role of MSCs in differentiation, transplantation, and immune response in various diseases.

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Causes and timing of death in patients with ARDS.

P. Steinberg, Gordon D Rubenfeld, Jennifer Hudson … (2005)

Since the early 1980s, case fatality of patients with ARDS has decreased, and explanations are unclear. Using identical definitions of ARDS and organ failure, we analyzed consecutive cohorts of patients meeting syndrome criteria at our institution in 1982 (n = 46), 1990 (n = 112), 1994 (n = 99), and 1998 (n = 205) to determine causes and timing of death. Overall case fatality has decreased from 68% in 1981-1982 to a low of 29% in 1996, plateauing since the mid-1990s (p = 0.001 for trend). Sepsis syndrome with multiple organ failure remains the most common cause of death (30 to 50%), while respiratory failure causes a small percentage (13 to 19%) of deaths. The distribution of causes of death has not changed over time. There was no change in the timing of death during the study periods: 26 to 44% of deaths occurred early ( 72 h after ARDS onset). However, the increased survival over the past 2 decades is entirely accounted for by patients who present with trauma and other risk factors for their ARDS, while survival for those patients whose risk factor is sepsis has not changed. Additionally, withdrawal of life support in these patients is now occurring at our institution significantly more frequently than in the past, and median time until death has decreased in patients who have support withdrawn. While these results do not explain the overall case fatality decline in ARDS, they do indicate that sepsis syndrome remains the leading cause of death and suggest that future therapies to improve survival be targeted at reducing the complications of sepsis.

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Mesenchymal stem cells-derived exosomal microRNAs contribute to wound inflammation.

Haojie Hao, Dongdong Ti, Xiaobing Fu … (2016)

Clinical and experimental studies have highlighted the significance of inflammation in coordinating wound repair and regeneration. However, it remains challenging to control the inflammatory response and tolerance at systemic levels without causing toxicity to injured tissues. Mesenchymal stem cells (MSCs) possess potent immunomodulatory properties and facilitate tissue repair by releasing exosomes, which generate a suitable microenvironment for inflammatory resolution. Exosomes contain several effective bioactive molecules and act as a cell-cell communication vehicle to influence cellular activities in recipient cells. During this process, the horizontal transfer of exosomal microRNAs (miRNAs) to acceptor cells, where they regulate target gene expression, is of particular interest for understanding the basic biology of inflammation ablation, tissue homeostasis, and development of therapeutic approaches. In this review, we describe a signature of three specific miRNAs (miR-21, miR-146a, and miR-181) present in human umbilical cord MSC-derived exosomes (MSC-EXO) identified microarray chip analysis and focus on the inflammatory regulatory functions of these immune-related miRNAs. We also discuss the potential mechanisms contributing to the resolution of wound inflammation and tissue healing.

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Author and article information

Contributors

Xingqi Deng

Journal

Journal ID (nlm-ta): PeerJ

Journal ID (iso-abbrev): PeerJ

Journal ID (publisher-id): peerj

Journal ID (pmc): peerj

Title: PeerJ

Publisher: PeerJ Inc. (San Diego, USA )

ISSN (Electronic): 2167-8359

Publication date (Electronic): 18 September 2020

Publication date Collection: 2020

Volume: 8

Electronic Location Identifier: e9928

Affiliations

[1 ]South Hospital of the Sixth People’s Hospital Affiliated to Shanghai Jiaotong University , Shanghai, China

[2 ]Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital , Shanghai, China

Article

Publisher ID: 9928

DOI: 10.7717/peerj.9928

PMC ID: 7505076

PubMed ID: 32999767

SO-VID: 90725c11-4649-469a-94d5-f5779267fa79

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

History

Date received : 23 January 2020

Date accepted : 21 August 2020

Funding

Funded by: Fengxian District Science and Technology Committee of Shanghai Municipality

Award ID: 20171019

Funded by: Seed Fund Project of Shanghai University of Medicine & Health Sciences

This work was supported by the Science and Technology Development Fund Project of the Fengxian District Science and Technology Committee of Shanghai Municipality (20171019) and the Seed Fund Project of Shanghai University of Medicine & Health Sciences (NATURAL SCIENCE). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Mesenchymal stem cell exosomes reverse acute lung injury through Nrf-2/ARE and NF- κB signaling pathways

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Abstract

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Inflamed lung in vitro co-culture models

Most cited references 8

Mesenchymal stem cells.

Causes and timing of death in patients with ARDS.

Mesenchymal stem cells-derived exosomal microRNAs contribute to wound inflammation.

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