Apparent Yield Stress of Sputum as a Relevant Biomarker in Cystic Fibrosis

Ghanem, Rosy; Roquefort, Philippe; Ramel, Sophie; Laurent, Véronique; Haute, Tanguy; Gall, Tony Le; Aubry, Thierry; Montier, Tristan

doi:10.3390/cells10113107

Cited by 12 publications

(10 citation statements)

References 38 publications

(40 reference statements)

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“…These results are in agreement with previous literature, where the viscosity of CF sputum was shown to be higher than healthy controls. 44 …”

Section: Resultsmentioning

confidence: 99%

“…These results are in agreement with previous literature, where the viscosity of CF sputum was shown to be higher than healthy controls. 44 Biofilm formation in airway mimicking media is stable for at least 30 days of media storage at 4°C. Biofilm formation of PAO1 was measured over a month in the developed media stored at 4°C to test the stability of the airway mimicking media.…”

Section: Cf Media Becomes Viscous During Infection Reflecting Propert...mentioning

confidence: 99%

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Development of liquid culture media mimicking the conditions of sinuses and lungs in cystic fibrosis and health

et al. 2022

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The respiratory tract is a compartmentalised and heterogenous environment. The nasopharynx and sinuses of the upper airways have distinct properties from the lungs and these differences may shape bacterial adaptation and evolution. Upper airway niches act as early colonisation sites for respiratory bacterial pathogens, including those, such as Pseudomonas aeruginosa, that can go on to establish chronic infection of the lungs in people with cystic fibrosis (CF). Despite the importance of upper airway environments in facilitating early adaptation to host environments, currently available in vitro models for study of respiratory infection in CF focus exclusively on the lungs. Furthermore, animal models, widely used to bridge the gap between in vitro systems and the clinical scenario, do not allow the upper and lower airways to be studied in isolation. We have developed a suite of culture media reproducing key features of the upper and lower airways, for the study of bacterial adaptation and evolution in different respiratory environments. For both upper and lower airway-mimicking media, we have developed formulations that reflect airway conditions in health and those that reflect the altered environment of the CF respiratory tract. Here, we describe the development and validation of these media and their use for study of genetic and phenotypic adaptations in P. aeruginosa during growth under upper or lower airway conditions in health and in CF.

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“…These results are in agreement with previous literature, where the viscosity of CF sputum was shown to be higher than healthy controls. 44 …”

Section: Resultsmentioning

confidence: 99%

Section: Cf Media Becomes Viscous During Infection Reflecting Propert...mentioning

confidence: 99%

Development of liquid culture media mimicking the conditions of sinuses and lungs in cystic fibrosis and health

et al. 2022

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“…Additionally, the viscoelastic properties of the CF and healthy mucus-like hydrogels developed herein were within the same order of magnitude as the viscoelastic properties of CF and healthy airway mucus that have been analyzed and reported in literature. Recent sources have found that healthy and CF airway mucus have storage moduli within the range of 0.2 Pa to 93 Pa and loss moduli within the range of 0.1 Pa to 19 Pa 6,7 . The hydrogels developed here recapitulate the key differences in viscoelastic properties, mucin concentration, and solids concentration in physiological CF and healthy airway mucus.…”

Section: Discussionmentioning

confidence: 99%

Modeling Cystic Fibrosis Chronic Infection Using Engineered Mucus-like Hydrogels

O’Brien,

Spencer,

Jafari

et al. 2023

Preprint

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The airway mucus of patients with cystic fibrosis has altered properties which create a microenvironment primed for chronic infections that are difficult to treat. These complex polymicrobial airway infections and corresponding mammalian-microbe interactions are challenging to modelin vitro. Here, we report the development of mucus-like hydrogels with varied compositions and viscoelastic properties reflecting differences between healthy and cystic fibrosis airway mucus. Models of cystic fibrosis and healthy airway microenvironments were created by combining the hydrogels with relevant pathogens, human bronchial epithelial cells, and an antibiotic. Notably, pathogen antibiotic resistance was not solely dependent on the altered properties of the mucus-like hydrogels but was also influenced by culture conditions including microbe species, monomicrobial or polymicrobial culture, and the presence of epithelial cells. Additionally, the cystic fibrosis airway model showed the ability to mimic features characteristic of chronic cystic fibrosis airway infections including sustained polymicrobial growth and increased antibiotic tolerance.

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“…Altogether, the results obtained from a dose escalation study (Figure S7) suggest that, although they are more sensitive than GL67A, CholP-based lipoplexes may retain some transfection efficiency under CF relevant conditions. This also suggests the requirement to further optimize CholP formulation, especially as regards its content in DP5K, and to investigate more complex cell culture models [70,71]. (ii) Considering bacterial infections that occur in the airways of CF patients, additional antibacterial properties of cationic lipids [18] or polymers [72] might be useful for CF lung gene therapy applications.…”

Section: Discussionmentioning

confidence: 99%

Aerosol-Mediated Non-Viral Lung Gene Therapy: The Potential of Aminoglycoside-Based Cationic Liposomes

et al. 2021

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Aerosol lung gene therapy using non-viral delivery systems represents a credible therapeutic strategy for chronic respiratory diseases, such as cystic fibrosis (CF). Progress in CF clinical setting using the lipidic formulation GL67A has demonstrated the relevance of such a strategy while emphasizing the need for more potent gene transfer agents. In recent years, many novel non-viral gene delivery vehicles were proposed as potential alternatives to GL67 cationic lipid. However, they were usually evaluated using procedures difficult or even impossible to implement in clinical practice. In this study, a clinically-relevant administration protocol via aerosol in murine lungs was used to conduct a comparative study with GL67A. Diverse lipidic compounds were used to prepare a series of formulations inspired by the composition of GL67A. While some of these formulations were ineffective at transfecting murine lungs, others demonstrated modest-to-very-efficient activities and a series of structure-activity relationships were unveiled. Lipidic aminoglycoside derivative-based formulations were found to be at least as efficient as GL67A following aerosol delivery of a luciferase-encoding plasmid DNA. A single aerosol treatment with one such formulation was found to mediate long-term lung transgene expression, exceeding half the animal’s lifetime. This study clearly supports the potential of aminoglycoside-based cationic lipids as potent GL67-alternative scaffolds for further enhanced aerosol non-viral lung gene therapy for diseases such as CF.

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Apparent Yield Stress of Sputum as a Relevant Biomarker in Cystic Fibrosis

Cited by 12 publications

References 38 publications

Development of liquid culture media mimicking the conditions of sinuses and lungs in cystic fibrosis and health

Development of liquid culture media mimicking the conditions of sinuses and lungs in cystic fibrosis and health

Modeling Cystic Fibrosis Chronic Infection Using Engineered Mucus-like Hydrogels

Aerosol-Mediated Non-Viral Lung Gene Therapy: The Potential of Aminoglycoside-Based Cationic Liposomes

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