Lung mesenchymal stem cells-derived extracellular vesicles attenuate the inflammatory profile of Cystic Fibrosis epithelial cells

Zulueta, Aı́da; Colombo, M.; Peli, Valeria; Falleni, Monica; Tosi, Delfina; Ricciardi, Mario; Baisi, Alessandro; Bulfamante, Gaetano; Chiaramonte, R.; Caretti, Anna

doi:10.1016/j.cellsig.2018.07.015

Cited by 36 publications

(34 citation statements)

References 45 publications

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“…A recent study identified proinflammatory signatures in respiratory vesicles from a small number of PWCF 8 highlighting the potential of EVs in modulating inflammation in CF. 9 We hypothesised that EVs released from CF lung epithelial cells play a role in regulating leukocyte migration into the CF airways and may help understand disease pathogenesis in CF. In this study, we employed comparative proteomics to characterise the global activity and protein composition of EV's released from CF airway cell lines and present in the bronchoalveolar lavage fluid (BALF) from PWCF.…”

Section: Why Read On?mentioning

confidence: 99%

Increased extracellular vesicles mediate inflammatory signalling in cystic fibrosis

Useckaite

Ward

Trappe

et al. 2020

Thorax

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RationaleMutations in the cystic fibrosis transmembrane regulator (CFTR) gene form the basis of cystic fibrosis (CF). There remains an important knowledge gap in CF as to how diminished CFTR activity leads to the dominant inflammatory response within CF airways.ObjectivesTo investigate if extracellular vesicles (EVs) contribute to inflammatory signalling in CF.MethodsEVs released from CFBE41o-, CuFi-5, 16HBE14o- and NuLi-1 cells were characterised by nanoparticle tracking analysis (NTA). EVs isolated from bronchoalveolar lavage fluid (BALF) from 30 people with CF (PWCF) were analysed by NTA and mass spectrometry and compared with controls. Neutrophils were isolated from the blood of 8 PWCF to examine neutrophil migration in the presence of CFBE41o- EVs.ResultsA significantly higher level of EVs were released from CFBE41o- (p<0.0001) and CuFi-5 (p=0.0209) relative to control cell lines. A significantly higher level of EVs were detected in BALF of PWCF, in three different age groups relative to controls (p=0.01, 0.001, 0.002). A significantly lower level of EVs were released from CFBE41o- (p<0.001) and CuFi-5 (p=0.0002) cell lines treated with CFTR modulators. Significant changes in the protein expression of 126 unique proteins was determined in EVs obtained from the BALF of PWCF of different age groups (p<0.001–0.05). A significant increase in chemotaxis of neutrophils derived from PWCF was observed in the presence of CFBE41o EVs (p=0.0024) compared with controls.ConclusionThis study demonstrates that EVs are produced in CF airway cells, have differential protein expression at different ages and drive neutrophil recruitment in CF.

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Section: Why Read On?mentioning

confidence: 99%

Increased extracellular vesicles mediate inflammatory signalling in cystic fibrosis

Useckaite

Ward

Trappe

et al. 2020

Thorax

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“…Studies have found that MSC secrete different types of extracellular vesicles (EV) believed to account for much of their therapeutic effects [124][125][126][127]. Additionally, more recent reports have explored the role of released EV from MSC as a potential therapeutic application for controlling inflammation in Cystic Fibrosis [128]. Zulueta and colleagues showed that treatment of IB3-1 CF cell line, (an in vitro human model of CF), with EV derived from human lung MSC under basal and inflammatory conditions (TNFα stimulation) downregulated transcription and protein expression of pro-inflammatory cytokines IL-1β, IL-8, IL-6 and upregulated the mRNA expression of PPARγ (a transcription factor controlling anti-inflammatory and antioxidant mechanisms via NF-kB and HO-1).…”

Section: Mesenchymal Stromal Cells (Msc)mentioning

confidence: 99%

Cell-Based Therapeutic Approaches for Cystic Fibrosis

Duchesneau

Waddell

Karoubi

2020

IJMS

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Cystic Fibrosis (CF) is a chronic autosomal recessive disease caused by defects in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Cystic Fibrosis affects multiple organs but progressive remodeling of the airways, mucus accumulation, and chronic inflammation in the lung, result in lung disease as the major cause of morbidity and mortality. While advances in management of CF symptoms have increased the life expectancy of this devastating disease, and there is tremendous excitement about the potential of new agents targeting the CFTR molecule itself, there is still no curative treatment. With the recent advances in the identification of endogenous airway progenitor cells and in directed differentiation of pluripotent cell sources, cell-based therapeutic approaches for CF have become a plausible treatment method with the potential to ultimately cure the disease. In this review, we highlight the current state of cell therapy in the CF field focusing on the relevant autologous and allogeneic cell populations under investigation and the challenges associated with their use. In addition, we present advances in induced pluripotent stem (iPS) cell approaches and emerging new genetic engineering methods, which have the capacity to overcome the current limitations hindering cell therapy approaches.

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“…Noteworthy, we found that MSCs-derived EVs treatment partially restored PPARγ signaling in CF deficient cells, accordingly to the results of Bonfield's group. Hence, we proposed the modulation of PPARγ axis and its down-stream effectors (NF-κB and HO-1) as a possible mechanism supporting the anti-inflammatory effects of MSCs-derived EVs in CF [74]. Data by our and Bonfield's group suggest that the lung MSCs compartment could be immunologically impaired in CF, thus contributing to maintain the unresolved pulmonary inflammation.…”

Section: Mesenchymal Stem Cells As Anti-inflammatory Therapy In Cystimentioning

confidence: 83%

Lights and Shadows in the Use of Mesenchymal Stem Cells in Lung Inflammation, a Poorly Investigated Topic in Cystic Fibrosis

Caretti

Peli

Colombo

et al. 2019

Cells

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Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic stem cells residing in many tissues, including the lung. MSCs have long been regarded as a promising tool for cell-based therapy because of their ability to replace damaged tissue by differentiating into the resident cell and repopulating the injured area. Their ability to release soluble factors and extracellular vesicles has emerged as crucial in the resolution of inflammation and injury. There is a growing literature on the use of MSCs and MSC secretome to hamper inflammation in different lung pathologies, including: asthma, pneumonia, acute lung injury (ALI), pulmonary hypertension, and chronic obstructive pulmonary disease (COPD). However, their potential therapeutic role in the context of Cystic Fibrosis (CF) lung inflammation is still not fully characterized. CF morbidity and mortality are mainly due to progressive lung dysfunction. Lung inflammation is a chronic and unresolved condition that triggers progressive tissue damage. Thus, it becomes even more important to develop innovative immunomodulatory therapies aside from classic anti-inflammatory agents. Here, we address the main features of CF and the implications in lung inflammation. We then review how MSCs and MSC secretome participate in attenuating inflammation in pulmonary pathologies, emphasizing the significant potential of MSCs as new therapeutic approach in CF.

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Lung mesenchymal stem cells-derived extracellular vesicles attenuate the inflammatory profile of Cystic Fibrosis epithelial cells

Cited by 36 publications

References 45 publications

Increased extracellular vesicles mediate inflammatory signalling in cystic fibrosis

Increased extracellular vesicles mediate inflammatory signalling in cystic fibrosis

Cell-Based Therapeutic Approaches for Cystic Fibrosis

Lights and Shadows in the Use of Mesenchymal Stem Cells in Lung Inflammation, a Poorly Investigated Topic in Cystic Fibrosis

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