Anti-Inflammatory and Immunomodulatory Role of Bone Marrow-Derived MSCs in Mice with Acute Lung Injury

Abdelmoneim, Mohamed; El-Naenaeey, El-Sayed Y; Abd-Allah, Somia H.; Gharib, Ahlam A.; Alhussein, Mona; Abo-Alella, Doaa; Abdelghany, Eman M.A.; Fathy, Maha A.; Hussein, Samia

doi:10.1089/jir.2020.0073

Cited by 6 publications

(6 citation statements)

References 27 publications

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“…[ 38,39 ] More importantly, Abdelmoneim and colleagues reported that systemic BMMSCs injection significantly inhibited inflammation and modulated the immune system in LPS‐induced acute lung injury in mice. [ 40 ] Similarly, Soliman and colleagues found that BMMSCs also significantly suppressed the endotoxin‐induced systemic inflammatory response in rats with ALI. [ 41 ] However, as cell therapy, BMMSCs have some weaknesses that limit their treatment effects in clinical.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow mesenchymal stem cells‐derived exosomes ameliorate LPS‐induced acute lung injury by miR‐223‐regulated alveolar macrophage M2 polarization

Xu,

Nie,

Deng

et al. 2023

J Biochem & Molecular Tox

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Numerous studies have shown that the M2 polarization of alveolar macrophages (AM) plays a protective role in acute lung injury (ALI). Mesenchymal stem cells (MSCs) secreted exosomes have been reported to be involved in inflammatory diseases by the effects of polarized M1/M2 macrophage populations. However, whether bone marrow mesenchymal stem cells (BMMSCs) derived exosomes could protect from ALI and its mechanisms are still unclear. Here, we explored the role of exosomes from BMMSC in rat AM polarization and the lipopolysaccharide‐ (LPS‐) induced ALI rat model. Furthermore, the levels of exosomal miR‐223 in BMMSCs were measured by RT‐qPCR. Additionally, miR‐223 mimics and its inhibitors were used to verify the vital role of miR‐223 of BMMSCs‐derived exosomes in the polarization of M2 macrophages. The results showed that BMMSCs‐derived exosomes were taken up by the AM. Exosomes derived from BMMSCs promoted M2 polarization of AM in vitro. BMMSCs exosomes effectively mitigated pathological injuries, lung edema, and the inflammation of rats from LPS‐induced ALI, accompanied by an increase of M2 polarization of AM in lung tissue. Interestingly, we also found that miR‐223 was enriched in BMMSCs‐derived exosomes, and overexpression of miR‐223 in BMMSCs‐derived exosomes promoted M2 polarization of AM while depressing miR‐223 showed opposite effects in AM. The present study demonstrated that BMMSCs‐derived exosomes triggered alveolar M2 polarization to improve inflammation by transferring miR‐223, which may provide new therapeutic strategies in ALI.

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Section: Discussionmentioning

confidence: 99%

Bone marrow mesenchymal stem cells‐derived exosomes ameliorate LPS‐induced acute lung injury by miR‐223‐regulated alveolar macrophage M2 polarization

Xu,

Nie,

Deng

et al. 2023

J Biochem & Molecular Tox

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“…In ammatory cell in ltration and massive production of in ammatory factors are important features of sepsis-induced acute lung injury (ALI) [20,21]. In ltration of in ammatory cells in lung tissue can release large amounts of in ammatory cytokines, such as TNF-α and IL-6, which cause damage to alveolar epithelial cells, disruption of alveolar structure, increased permeability of alveolar epithelial cells, impaired lung barrier function, eventually pulmonary edema develops [22]. NF-kB signaling pathway has an important role in sepsis-induced ALI and can activate the transcription of multiple in ammatory genes [23], thus aggravating sepsis induced lung injury [24] and also regulates the expression of epithelial cell tight junction proteins to impair epithelial cell barrier function [25].…”

Section: Discussionmentioning

confidence: 99%

β-sitosterol improves the permeability of lung epithelial cells by inhibiting the NF-kB pathway

Chen

Ren

et al. 2023

Preprint

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Objective: To investigate the mechanism of the protective effect of beta-sitosterol (BS) on sepsis-induced lung injury. METHODS: A mouse model of sepsis-induced lung injury was established by cecum ligation and puncture (CLP). The murine lung epithelial (MLE-12) cells injury model was established by challenging LPS. Evans blue staining, lung wet/dry mass ratio (W/D), and the total protein concentration in bronchoalveolar lavage fluid (BALF) were used to assess the changes in lung tissue permeability. HE staining was performed to observe the histopathological changes in lung tissues. ELISA was examined to determine IL-6 and TNF-α inflammatory factors in each group of lung tissues and cells. The protein levels of claudin-4, claudin-5, Bcl-2, Bax, p65 and p-p65 were detected by western blotting or immunofluorescence. Fluorescein isothiocyanate (FITC)-dextran extravasation as a measure of MLE-12 cells permeability. RESULTS: BS attenuated lung tissue pathological changes caused by sepsis, reduced the level of inflammatory factors and decreased the permeability of lung tissue and MLE-12 cells. Moreover, BS inhibited NF-kB signaling pathway to upregulate tight junction proteins claudin-4 and claudin-5 thereby improving septic lung epithelial cell permeability. CONCLUSION: BS reduces the level of inflammatory factors by inhibiting NF-kB signaling pathway and regulates the expression of tight junction proteins claudin-4 and claudin-5 to improve the barrier function of lung epithelial cells, thus improving lung injury caused by sepsis.

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“…However, the mechanisms of MSC and IEL recruitment are unclear. Although MSCs have an immunomodulatory effect in ALI, 28,29 we propose that they not only have an immunomodulatory effect but also alter the intestinal microbiome in a manner that promotes barrier integrity.…”

Section: Introductionmentioning

confidence: 89%

Immunosuppressive effect of mesenchymal stem cells on lung and gut CD8⁺ T cells in lipopolysaccharide‐induced acute lung injury in mice

Zhu

Feng

et al. 2021

Cell Proliferation

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Objectives Acute lung injury (ALI) not only affects pulmonary function but also leads to intestinal dysfunction, which in turn contributes to ALI. Mesenchymal stem cell (MSC) transplantation can be a potential strategy in the treatment of ALI. However, the mechanisms of synergistic regulatory effects by MSCs on the lung and intestine in ALI need more in‐depth study. Materials and methods We evaluated the therapeutic effects of MSCs on the murine model of lipopolysaccharide (LPS)‐induced ALI through survival rate, histopathology and bronchoalveolar lavage fluid. Metagenomic sequencing was performed to assess the gut microbiota. The levels of pulmonary and intestinal inflammation and immune response were assessed by analysing cytokine expression and flow cytometry. Results Mesenchymal stem cells significantly improved the survival rate of mice with ALI, alleviated histopathological lung damage, improved intestinal barrier integrity, and reduced the levels of inflammatory cytokines in the lung and gut. Furthermore, MSCs inhibited the inflammatory response by decreasing the infiltration of CD8+ T cells in both small‐intestinal lymphocytes and Peyer's patches. The gut bacterial community diversity was significantly altered by MSC transplantation. Furthermore, depletion of intestinal bacterial communities with antibiotics resulted in more severe lung and gut damages and mortality, while MSCs significantly alleviated lung injury due to their immunosuppressive effect. Conclusions The present research indicates that MSCs attenuate lung and gut injury partly via regulation of the immune response in the lungs and intestines and gut microbiota, providing new insights into the mechanisms underlying the therapeutic effects of MSC treatment for LPS‐induced ALI.

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Anti-Inflammatory and Immunomodulatory Role of Bone Marrow-Derived MSCs in Mice with Acute Lung Injury

Cited by 6 publications

References 27 publications

Bone marrow mesenchymal stem cells‐derived exosomes ameliorate LPS‐induced acute lung injury by miR‐223‐regulated alveolar macrophage M2 polarization

Bone marrow mesenchymal stem cells‐derived exosomes ameliorate LPS‐induced acute lung injury by miR‐223‐regulated alveolar macrophage M2 polarization

β-sitosterol improves the permeability of lung epithelial cells by inhibiting the NF-kB pathway

Immunosuppressive effect of mesenchymal stem cells on lung and gut CD8⁺ T cells in lipopolysaccharide‐induced acute lung injury in mice

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Anti-Inflammatory and Immunomodulatory Role of Bone Marrow-Derived MSCs in Mice with Acute Lung Injury

Cited by 6 publications

References 27 publications

Bone marrow mesenchymal stem cells‐derived exosomes ameliorate LPS‐induced acute lung injury by miR‐223‐regulated alveolar macrophage M2 polarization

Bone marrow mesenchymal stem cells‐derived exosomes ameliorate LPS‐induced acute lung injury by miR‐223‐regulated alveolar macrophage M2 polarization

β-sitosterol improves the permeability of lung epithelial cells by inhibiting the NF-kB pathway

Immunosuppressive effect of mesenchymal stem cells on lung and gut CD8+ T cells in lipopolysaccharide‐induced acute lung injury in mice

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Immunosuppressive effect of mesenchymal stem cells on lung and gut CD8⁺ T cells in lipopolysaccharide‐induced acute lung injury in mice