Identification of early events in nitrogen mustard pulmonary toxicity that are independent of infiltrating inflammatory cells using precision cut lung slices

Bellomo, Alyssa; Herbert, Julia; Kudlak, Melissa J.; Laskin, Jeffrey D.; Gow, Andrew J.; Laskin, Debra L.

doi:10.1016/j.taap.2024.116941

Cited by 3 publications

(1 citation statement)

References 66 publications

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“…Such a biosensor can provide a tool for understanding of toxicity of a variety of environmental compounds. Additionally, another study found that the effects of nitrogen mustard exposure that drive pulmonary toxicity appear to be independent of immune cell trafficking to the lungs [ 245 ].…”

Section: Introductionmentioning

confidence: 99%

Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery

Koziol-White,

Gebski,

Cao

et al. 2024

Respir Res

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Precision Cut Lung Slices (PCLS) have emerged as a sophisticated and physiologically relevant ex vivo model for studying the intricacies of lung diseases, including fibrosis, injury, repair, and host defense mechanisms. This innovative methodology presents a unique opportunity to bridge the gap between traditional in vitro cell cultures and in vivo animal models, offering researchers a more accurate representation of the intricate microenvironment of the lung. PCLS require the precise sectioning of lung tissue to maintain its structural and functional integrity. These thin slices serve as invaluable tools for various research endeavors, particularly in the realm of airway diseases. By providing a controlled microenvironment, precision-cut lung slices empower researchers to dissect and comprehend the multifaceted interactions and responses within lung tissue, thereby advancing our understanding of pulmonary pathophysiology.

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Section: Introductionmentioning

confidence: 99%

Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery

Koziol-White,

Gebski,

Cao

et al. 2024

Respir Res

View full text Add to dashboard Cite

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Precision cut lung slices: an innovative tool for lung transplant research

Kollareth,

Sharma

2024

Front. Immunol.

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Lung ischemia-reperfusion injury (IRI), a common complication after lung transplantation (LTx), plays a crucial role in both primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD) thereby adversely impacting the clinical outcomes in these patient cohorts. Lung IRI is characterized by several molecular events including immune cell infiltration, reactive oxygen species (ROS) generation, calcium overload, inflammation and various forms of cell death pathways. Currently, no therapeutic agents are available to clinically prevent lung IRI. While animal and cell culture models are highly valuable in understanding the pathophysiology of lung IRI, they may not completely recapitulate the complexity of human lung tissue pathology. This limitation necessitates the requirement for developing innovative preclinical human research tools that can supplement available scientific modalities. Emerging evidence suggests that precision-cut lung slices (PCLS) have become an indispensable tool in scientific research to study lung biology in an ex vivo tissue system. Recent studies using PCLS have investigated lung diseases including asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Although PCLS can be successfully employed to determine the deleterious events in the pathogenesis of lung IRI, including cell-cell interactions as well as hallmarks of inflammation and oxidative stress-dependent pathways, detailed studies employing PCLS to decipher these molecular events in post-LTx injury are currently limited. This review focuses on the applicability and unexplored potential of PCLS as a powerful tool in lung IRI research for understanding the pathophysiology and consequent development of new therapeutic modalities.

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Assessment of Imatinib Anti-Remodeling Activity on a Human Precision Cut Lung Slices Model

Bozzini,

Bozza,

Bagnera

et al. 2024

IJMS

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Recent studies have emphasized the critical role of alteration in cellular plasticity in the development of fibrotic disorders, particularly pulmonary fibrosis, prompting further investigation into molecular mechanisms and therapeutic approaches. In this context, Precision Cut Lung Slices (PCLSs) emerge as a valuable ex vivo research tool. The process of PCLSs generation preserves most features of the naïve lung tissue, such as its architecture and complex cellular composition. We previously stimulated normal lung PCLSs with two different stimuli (fibrotic cocktail, composed by platelet lysate and TGFβ, or neutrophil extracellular traps) and we observed a significant elevation of Epithelial–Mesenchymal Transition (EMT) markers from 24 h to 72 h of culture. The aim of our work was to exploit this PCLSs based ex vivo model of EMT, to evaluate the effect of imatinib, an old tyrosine kinase inhibitor with reported anti-remodeling activities in vitro and in animal models. Imatinib treatment significantly decreased α-SMA and collagen expression already starting from 24 h on stimulated PCLS. Imatinib showed a significant toxicity on unstimulated cells (3-fold increase in ACTA2 expression levels at 24 h, 1.5-fold increase in COL1A1 expression levels at 24 h, 2-fold increase in COL3A1 expression levels at 72 h). Further evaluations on specific cell lines pointed out that drug effects were mainly directed towards A549 and LFs. In conclusion, our model confirms the anti-remodeling activity of imatinib but suggests that its direct delivery to alveolar epithelial cells as recently attempted by inhalatory preparation of the drug might be associated with a non-negligible epithelial cell toxicity.

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Identification of early events in nitrogen mustard pulmonary toxicity that are independent of infiltrating inflammatory cells using precision cut lung slices

Cited by 3 publications

References 66 publications

Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery

Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery

Precision cut lung slices: an innovative tool for lung transplant research

Assessment of Imatinib Anti-Remodeling Activity on a Human Precision Cut Lung Slices Model

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