In vitro modelling of bacterial pneumonia: a comparative analysis of widely applied complex cell culture models

FEMS Microbiology Reviews, Год журнала: 2024, Номер 48(2)

Опубликована: Фев. 26, 2024

Abstract Bacterial pneumonia greatly contributes to the disease burden and mortality of lower respiratory tract infections among all age groups risk profiles. Therefore, laboratory modelling bacterial remains important for elucidating complex host–pathogen interactions determine drug efficacy toxicity. In vitro cell culture enables creation high-throughput, specific models in a tightly controlled environment. Advanced human specifically, can bridge research gap between classical two-dimensional animal models. This review provides an overview current status development cellular study infections, with focus on air–liquid interface models, spheroid, organoid, lung-on-a-chip For wide scale, comparative literature search, we selected six clinically highly relevant bacteria (Pseudomonas aeruginosa, Mycoplasma pneumoniae, Haemophilus influenzae, Mycobacterium tuberculosis, Streptococcus Staphylococcus aureus). We reviewed lines that are commonly used, as well trends discrepancies methodology, ranging from infection parameters assay read-outs. also highlighted importance model validation data transparency guiding field towards more

Язык: Английский

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Advances of microfluidic lung chips for assessing atmospheric pollutants exposure

Environment International, Год журнала: 2023, Номер 172, С. 107801 - 107801

Опубликована: Фев. 1, 2023

Atmospheric pollutants, including particulate matters, nanoparticles, bioaerosols, and some chemicals, have posed serious threats to the environment human's health. The lungs are responsible organs for providing interface between circulatory system external environment, where pollutant particles can deposit or penetrate into bloodstream circulation. Conventional studies decipher mechanism underlying air pollution human health quite limited, due lack of reliable models that reproduce in vivo features lung tissues after pollutants exposure. In past decade, advanced near-to-native chips, combining cell biology with bioengineered technology, present a new strategy atmospheric assessment narrow gap 2D culture animal models. this review, key artificial chips cutting-edge technologies chip manufacture introduced. recent progresses exposure summarized highlighted. We further discuss current challenges future opportunities development their potential utilities associated toxicity testing drug screening.

Язык: Английский

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Functioning human lung organoids model pulmonary tissue response from carbon nanomaterial exposures

Nano Today, Год журнала: 2024, Номер 56, С. 102254 - 102254

Опубликована: Апрель 4, 2024

Human lung organoids (HLOs) are increasingly used to model development and infectious diseases, however their ability recapitulate functional pulmonary tissue response nanomaterial (NM) exposures has yet be demonstrated. Here, we established a organoid exposure that utilises microinjection present NMs into the lumen of organoids. Our assures efficient, reproducible controllable apical epithelium, emulating real-life human scenario. By comparing impact two well studied carbon-based NMs, graphene oxide sheets (GO) multi-walled carbon nanotubes (MWCNT), validated as tools for predicting NM-driven responses. In agreement with in vivo data, demonstrate MWCNT, but not GO, elicit adverse effects on organoids, leading pro-fibrotic phenotype. findings reveal capacity suitability HLOs hazard assessment aligned much sought-out 3Rs (animal research replacement, reduction, refinement) framework.

Язык: Английский

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Organoids and microphysiological systems: Promising models for accelerating AAV gene therapy studies

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Сен. 26, 2022

The FDA has predicted that at least 10-20 gene therapy products will be approved by 2025. surge in the development of such therapies can attributed to advent safe and effective delivery vectors as adeno-associated virus (AAV). enormous potential AAV been demonstrated its use over 100 clinical trials FDA's approval two AAV-based products. Despite success some settings, is still plagued issues related host immunity, recent studies have suggested may actually integrate into cell genome, raising concerns for genotoxicity. To better understand these develop means overcome them, preclinical model systems accurately recapitulate human physiology are needed. objective this review provide a brief overview current hurdles, discuss how 3D organoids, microphysiological systems, body-on-a-chip platforms could serve powerful models adopted stage, examples successful application answer critical questions regarding biology toxicity not answered using animal models. Finally, technical considerations while adopting study also discussed.

Язык: Английский

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Innovative three-dimensional models for understanding mechanisms underlying lung diseases: powerful tools for translational research

European Respiratory Review, Год журнала: 2023, Номер 32(169), С. 230042 - 230042

Опубликована: Июль 26, 2023

Chronic lung diseases result from alteration and/or destruction of tissue, inevitably causing decreased breathing capacity and quality life for patients. While animal models have paved the way our understanding pathobiology development therapeutic strategies disease management, their translational is limited. There is, therefore, a well-recognised need innovative in vitro to reflect chronic diseases, which will facilitate mechanism investigation advancement new treatment strategies. In last decades, lungs been modelled healthy diseased conditions using precision-cut slices, organoids, extracellular matrix-derived hydrogels lung-on-chip systems. These three-dimensional together provide wide spectrum applicability mimicry microenvironment. each system has its own limitations, advantages over traditional two-dimensional culture systems, or even models, increases value models. Generating advanced with increased not only benefit but should also shorten timelines required discovery generation therapeutics. This article summarises provides an outline European Respiratory Society research seminar “Innovative 3D mechanisms underlying diseases: powerful tools research”, held Lisbon, Portugal, April 2022. Current developed recapitulating are outlined discussed respect challenges associated them, efforts develop best practices model generation, characterisation utilisation state-of-the-art potential.

Язык: Английский

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On the path to predicting immune responses in the lung: Modeling the pulmonary innate immune system at the air-liquid interface (ALI)

European Journal of Pharmaceutical Sciences, Год журнала: 2023, Номер 191, С. 106596 - 106596

Опубликована: Сен. 26, 2023

Chronic respiratory diseases and infections are among the largest contributors to death globally, many of which still have no cure, including chronic obstructive pulmonary disorder, idiopathic fibrosis, syncytial virus others. Pulmonary therapeutics afford untapped potential for treating lung infection disease through direct delivery site action. However, ability innovate new therapeutic paradigms will rely on modeling human microenvironment key cellular interactions that drive disease. One feature is air-liquid interface (ALI). ALI techniques, using cell-culture inserts, organoids, microfluidics, precision slices (PCLS), rapidly developing; however, one major component these models lacking—innate immune cell populations. Macrophages, neutrophils, dendritic cells, others, represent populations, acting as first responders during or injury. Innate cells respond modulate stromal bridge gap between innate adaptive system, controlling bodies response foreign pathogens debris. In this article, we review current state culture systems with a focus suggest ways build add complexity relevant

Язык: Английский

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Human-Induced Pluripotent Stem Cell-Based Alveolus-on-Chip Model to Study Influenza Virus A Infection

Methods in molecular biology, Год журнала: 2025, Номер unknown, С. 225 - 235

Опубликована: Янв. 1, 2025

Язык: Английский

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Quantitative adverse outcome pathway modeling for cigarette-smoke-induced airway mucus hypersecretion. Part 1: adverse-outcome-pathway-based in vitro assessment with repeated exposure to whole cigarette smoke

Frontiers in Toxicology, Год журнала: 2025, Номер 7

Опубликована: Май 15, 2025

Adverse outcome pathway (AOP)-based chemical risk assessment is a promising tool for regulatory decision-making and typically used in toxicological assessments. However, it also holds potential pharmacological disease-related evaluations. The present study focuses on an AOP decreased lung function. Lung function normally robustly maintained by homeostatic capacity, but repeated chronic stimulation can disrupt this leading to impaired mucus hypersecretion. We developed AOP-based vitro method test the states that be reproduced exposing three-dimensionally cultured human bronchial epithelial cells (3D-HBECs) whole cigarette smoke (WCS). Over duration of 2 weeks, we repeatedly exposed 3D-HBECs from six different donors WCS times observe both acute phase responses (oxidative stress, epidermal growth factor receptor activation, SP1 activation) (intracellular production, goblet cell metaplasia/hyperplasia, hypersecretion) along AOP. Our results demonstrate although exposure induced biological all donors, there were interdonor differences, particularly timing amplitudes responses. All smokers do not exhibit phenotypic changes with same smoking duration, so variability likely reflects individual differences. anticipate our combined computational quantitative modeling (discussed Part 2) will become valuable assessing disease airborne materials inhalable products.

Язык: Английский

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Development and Characterization of a 96‐Well Exposure System for Safety Assessment of Nanomaterials

Small, Год журнала: 2023, Номер 19(23)

Опубликована: Март 15, 2023

Abstract In this study, a 96‐well exposure system for safety assessment of nanomaterials is developed and characterized using an air–liquid interface lung epithelial model. This designed sequential nebulization. Distribution studies verify the reproducible distribution over all 96 wells, with lower insert‐to‐insert variability compared to non‐sequential application. With first set chemicals (TritonX), drugs (Bortezomib), (silver nanoparticles (non‐)fluorescent crystalline nanocellulose), are performed human cells followed by quantification deposited mass cell viability. The offers time possibility exposing model in format, resulting high‐throughput rates, combined feature dosing. allows creating dose‐response curves generation more reliable cell‐based assay data many types applications, such as analysis. addition drugs, spherical shapes, but also morphologically complex nanostructures can be exposed sequentially high efficiency. new perspectives on vivo‐like animal‐free approaches chemical pharmaceutical assessment, line 3R principle replacing reducing animal experiments.

Язык: Английский

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3D (bio)printing of lungs: past, present, and future

European Respiratory Journal, Год журнала: 2022, Номер 61(1), С. 2200417 - 2200417

Опубликована: Окт. 20, 2022

The field of 3D bioprinting is rapidly evolving, and the lung not being left behind. Interdisciplinary advances in printing technology, bioink formulations, cell biology are moving closer towards faithfully recapitulating native human lung.https://bit.ly/3EL3XUe

Язык: Английский

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