Enhanced susceptibility of pediatric airway epithelium to respiratory syncytial virus infection DOI Creative Commons
Raymond J. Pickles, Gang Chen, Scott H. Randell

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(21)

Published: Oct. 31, 2024

Immature innate and adaptive immunity vulnerability of narrower airways to obstruction increase the susceptibility infants severe respiratory syncytial virus (RSV) disease. In this issue JCI, Zhao et al. illustrated greater intrinsic pediatric versus adult airway epithelial cells RSV-induced cytopathology. Using precision cut lung slices (PCLS) air-liquid interface (ALI) cell cultures, authors showed that impaired STAT3 activation in RSV-infected multiciliated increased apoptosis viral shedding, which enhanced spread infection. Bolstering treatment neonatal mice with inhibitors suppressed spread, suggesting enhancing may provide therapeutic benefit.

Language: Английский

Cold storage of human precision-cut lung slices in TiProtec preserves cellular composition and transcriptional responses and enables on-demand mechanistic studies DOI Creative Commons
M. Camila Melo-Narváez,

Fee Gölitz,

Eshita Jain

et al.

Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)

Published: Feb. 17, 2025

Language: Английский

Citations

1
Innate Immunity and Asthma Exacerbations: Insights From Human Models DOI
Jehan Alladina, Benjamin D. Medoff, Christina Schofield

et al.

Immunological Reviews, Journal Year: 2025, Volume and Issue: 330(1)

Published: March 1, 2025

ABSTRACT Asthma is a common chronic respiratory disease characterized by the presence of airway inflammation, hyperresponsiveness, and mucus hypersecretion. Repeated asthma exacerbations can lead to progressive remodeling irreversible airflow obstruction. Thus, understanding preventing are paramount importance. Although multiple endotypes exist, most often driven type 2 inflammation. New therapies that target specific mediators have been shown reduce frequency but incompletely effective in significant number asthmatics. Furthermore, it remains unknown whether current treatments sustained changes or if targeting additional pathways may be necessary achieve remission. Activation innate immunity initial event inflammatory sequence occurs during an exacerbation. However, there continue critical gaps our immune response exacerbating factors. In this review, we summarize role methods used study them. We also identify potential novel therapeutic targets for future areas investigation.

Language: Английский

Citations

1
Correction: Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery DOI Creative Commons
Cynthia Koziol‐White, Eric Gebski,

Gaoyaun Cao

et al.

Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 27, 2025

Language: Английский

Citations

0
Fibrosis in PCLS: comparing TGF-β and fibrotic cocktail DOI Creative Commons
Carlos Machahua, Thomas M. Marti, Patrick Dorn

et al.

Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 28, 2025

Fibrotic cocktail (FC) is a combination of pro-fibrotic and pro-inflammatory mediators that induces early fibrotic changes in organotypic lung models. We hypothesised transforming growth factor beta 1 (TGF-β1) alone effect similar to FC. Our aim was compare the effects TGF-β1 with FC human precision-cut slices (PCLS). PCLS from "healthy" tissue cancer patients undergoing surgery (n = 7) were incubated TGF-β1, or control for 72 h. Gene expression markers myofibroblasts differentiation, extracellular matrix (ECM), as well TGF-β receptors assessed (RT-qPCR). ECM proteins lysates supernatant by ELISA immunofluorescence. found significantly increased gene ACTA2, COL1A1, CCN2, VIM compared but also showed significant increase metalloproteinase (MMP) 7 control, while receptor 2 lower after control. fibronectin protein supernatants, type I collagen greater findings show consistent Compared treatment resulted reduced MMPs expression, potentially mitigating effects. Selecting specific stimuli may be preferable depending on research question time point interest fibrosis studies using PCLS.

Language: Английский

Citations

0
Analyzing Pathophysiology and Immune Cells and Their Cytokines and Mediators in Precision‐Cut Slices of the Murine Lung DOI Creative Commons

Michaela Tatcheff,

Carlos Eduardo Carvalho,

Jonas Willar

et al.

Current Protocols, Journal Year: 2025, Volume and Issue: 5(1)

Published: Jan. 1, 2025

Abstract Understanding the dynamic pathophysiology of diseases in lung, such as asthma and chronic asthma, obstructive pulmonary disease, lung cancer, is crucial for treatment, analysis, outcome these diseases. Unlike other traditional models, we suggest a protocol that sustainable reproducible offers different analysis methods while maintaining vivo architecture immune dynamics. This allows one to study pathophysiological changes, including changes cells, cytokines, mediators, 30 precision‐cut slices from single murine lung. To accomplish this, infused with 2.5% low‐melting‐point agarose precision‐cut‐sliced. Our method also supports cell culture refined medium stimulation clinically relevant stimuli, which helps clarify mechanisms disease. Evaluation samples their supernatant includes multiplex assays, ELISA, histology, immunohistochemistry. Additional sections are used extract RNA quantitative real‐time PCR sequencing and/or selected like flow cytometry. Using this method, obtained preserve disease allow comprehensive unlike already‐existing protocols. By retaining mechanisms, able see histological damage caused by each The results can be improve our understanding therapy options. © 2025 Author(s). Current Protocols published Wiley Periodicals LLC. Basic Protocol : Obtaining (PCLSs) Support 1 LL/2 treatment G‐418 solution 2 Murine model adenocarcinoma imaging 3 H&E staining PCLS 4 Measuring cytokines ELISA 5 cytotoxic activity conditioned 6 Analysis PCLSs 7 Flow cytometry cells isolated

Language: Английский

Citations

0
Inhibition of DLK1 regulates AT2 differentiation and alleviates established pulmonary fibrosis by upregulating TTF-1/CLDN6 DOI Creative Commons

Yinzhen Li,

Chen Zhou, Jiaxing Sun

et al.

Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)

Published: May 16, 2025

Language: Английский

Citations

0
A Novel In Vitro Primary Human Alveolar Model (AlveolAir™) for H1N1 and SARS-CoV-2 Infection and Antiviral Screening DOI Creative Commons
Cristiane Lopes,

Emilie Laurent,

Mireille Caul-Futy

et al.

Microorganisms, Journal Year: 2025, Volume and Issue: 13(3), P. 572 - 572

Published: March 3, 2025

Lower respiratory infections, mostly caused by viral or bacterial pathogens, remain a leading global cause of mortality. The differences between animal models and humans contribute to inefficiencies in drug development, highlighting the need for more relevant predictive, non-animal models. In this context, AlveolAir™, fully primary vitro 3D human alveolar model, was characterized demonstrated sustained presence type I (ATI) II (ATII) cells. This model exhibited functional barrier over 30-day period, evidenced high transepithelial electrical resistance (TEER). These findings were further validated tight junctions’ confocal microscopy low permeability Lucifer yellow, confirming AlveolAir™ as robust platform transport assays. Additionally, successful infections with H1N1 SARS-CoV-2 viruses achieved, antiviral treatments Baloxavir Remdesivir, respectively, effectively reduced replication. Interestingly, both infected only epithelial layer without replicating endothelial indicate assessing toxicity xenobiotics evaluating efficacy novel therapies.

Language: Английский

Citations

0
Epithelial Dysfunction in Congenital Diaphragmatic Hernia: Mechanisms, Models and Emerging Therapies DOI Creative Commons
Ophelia Aubert,

Olivia M. Dinwoodie,

Richard Wagner

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(10), P. 687 - 687

Published: May 9, 2025

Congenital diaphragmatic hernia (CDH) is a complex disorder whereby improper formation of the diaphragm allows herniation internal organs into thoracic cavity, resulting in pulmonary hypoplasia among other complications. Although epithelial dysfunction central to CDH pathology, relatively little attention has been paid underlying mechanisms orchestrating malfunction. Proinflammatory signaling downstream impaired mechanotransduction due utero lung compression elucidated drive cell phenotypes. This illustrated by reduction nuclear YAP and upregulation NF-kB models. In this review, we draw from recent findings using emerging technologies examine discuss role as and, crucially, sufficient driver recognition limitations genetic knockout models recapitulate such heterogenic etiologically complicated disease, alternative established nitrofen rat model, air–liquid interface (ALI) cultures, organoids ex vivo explants. Throughout, acknowledge importance involving mechanical modeling order faithfully disease. Finally, explore novel therapeutic strategies stem regenerative therapies precision medicine defining endotypes guide treatments.

Language: Английский

Citations

0
Cryopreservation of human lung tissue for 3D ex vivo analysis DOI Creative Commons
Nickolas Diodati, Ganlin Qu, Borna Mehrad

et al.

Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)

Published: May 15, 2025

Language: Английский

Citations

0
Local photo-crosslinking of native tissue matrix regulates cell function DOI Creative Commons
Donia W Ahmed,

Matthew L. Tan,

Jackson Gabbard

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 10, 2024

Abstract Within most tissues, the extracellular microenvironment provides mechanical cues that guide cell fate and function. Changes in matrix such as aberrant deposition, densification increased crosslinking are hallmarks of late-stage fibrotic diseases often lead to organ dysfunction. Biomaterials have been widely used mimic properties study However, initiation fibrosis has largely overlooked, due challenges recapitulating early lesions within native microenvironment. Using visible light mediated photochemistry, we induced local stiffening proteins ex vivo murine human tissue. In lung tissue epithelial lineage-traced mice, mimicked alveolar spreading, differentiation remodeling. inhibition cytoskeletal tension or integrin engagement reduced spreading differentiation, resulting dedifferentiation deposition. Our findings emphasize role remodeling early-stage implications for disease modeling applications other tissues.

Language: Английский

Citations

0