S-Glutathionylation-Controlled Apoptosis of Lung Epithelial Cells; Potential Implications for Lung Fibrosis DOI Creative Commons
Elizabeth M. Corteselli, Reem Aboushousha, Yvonne M. W. Janssen‐Heininger

et al.

Antioxidants, Journal Year: 2022, Volume and Issue: 11(9), P. 1789 - 1789

Published: Sept. 10, 2022

Glutathione (GSH), a major antioxidant in mammalian cells, regulates several vital cellular processes, such as nutrient metabolism, protein synthesis, and immune responses. In addition to its role defense, GSH controls biological processes through conjugation reactive cysteines post-translational modification known S-glutathionylation (PSSG). PSSG has recently been implicated the pathogenesis of multiple diseases including idiopathic pulmonary fibrosis (IPF). Hallmarks IPF include repeated injury alveolar epithelium with aberrant tissue repair, epithelial cell apoptosis fibroblast resistance apoptosis, accumulation extracellular matrix distortion normal lung architecture. Several studies have linked oxidative stress development progression IPF. Additionally, it suggested that loss homeostasis increased accompanied by release various metabolites, creates vicious cycle aggravates disease progression. this short review, we highlight some recent link potential implication metabolites secreted apoptotic cells.

Language: Английский

Advancements in preclinical human-relevant modeling of pulmonary vasculature on-chip DOI Creative Commons
Quoc Vo, Kambez H. Benam

European Journal of Pharmaceutical Sciences, Journal Year: 2024, Volume and Issue: 195, P. 106709 - 106709

Published: Jan. 19, 2024

Preclinical human-relevant modeling of organ-specific vasculature offers a unique opportunity to recreate pathophysiological intercellular, tissue-tissue, and cell-matrix interactions for broad range applications. Lung is particularly important due its involvement in genesis progression rare, debilitating disorders as well common chronic pathologies. Here, we provide an overview the latest advances development pulmonary vascular (PV) models using emerging microfluidic tissue engineering technology Organs-on-Chips (so-called PV-Chips). We first review currently reported PV-Chip systems their key features, then critically discuss major limitations reproducing vivo-seen disease-relevant cellularity, localization, microstructure. conclude by presenting efforts overcome such technical biological future directions.

Language: Английский

Citations

4
Respiratory System DOI
Molly H. Boyle, Jack R. Harkema,

Kristen J. Nikula

et al.

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 235 - 335

Published: Jan. 1, 2025

Language: Английский

Citations

0
Lung organoids in COPD: recent advances and future prospects DOI Creative Commons
Yajie Huo, Shengyang He, Yan Chen

et al.

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

Published: Feb. 28, 2025

Abstract Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway that characterized by progressive airflow limitation, high prevalence, and mortality rate. However, the specific mechanisms remain unclear, partly due to lack of robust data from in vitro experimental models animal do not adequately represent structure pathophysiology human lung. The recent advancement lung organoid culture systems has facilitated new avenues for investigation COPD. Lung organoids are derived adult stem cells, pluripotent or embryonic established through three-dimensional culture. They exhibit degree homology genetic consistency with tissues can better mimic lungs terms function compared other traditional models. This review will summarise generation process different cell sources their application COPD research, provide suggestions future research directions.

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
In vitro models to study viral-induced asthma exacerbation: a short review for a key issue DOI Creative Commons
R OLIVEIRA, Clément Droillard,

Gilles Devouassoux

et al.

Frontiers in Allergy, Journal Year: 2025, Volume and Issue: 6

Published: March 28, 2025

Asthma is a heterogenous inflammatory bronchial disease involving complex mechanisms, several pathways, and multiples cell-type networks. Bronchial inflammation associated to asthma consecutive multiple aggressions on epithelium, such as microbiologic, pollutant, antigenic agents, which are responsible for both T2 non-T2 responses further airway remodeling. Because physiopathology involves crosstalk between cell types from different origins (epithelial, mesenchymal, immune cells) numerous cellular effectors, no single and/or representative in vitro model suitable study the overall of this disease. In short review, we present discuss advantages limitations models decipher aspects virus-related exacerbation.

Language: Английский

Citations

0
Advanced In Vitro Lung Models for Drug and Toxicity Screening: The Promising Role of Induced Pluripotent Stem Cells DOI
Anabela Moreira, Michelle Müller, Pedro F. Costa

et al.

Advanced Biology, Journal Year: 2021, Volume and Issue: 6(2)

Published: Dec. 27, 2021

The substantial socioeconomic burden of lung diseases, recently highlighted by the disastrous impact coronavirus disease 2019 (COVID-19) pandemic, accentuates need for interventive treatments capable decelerating progression, limiting organ damage, and contributing to a functional tissue recovery. However, this is hampered lack accurate human research models, which currently fail reproduce pulmonary architecture biochemical environment. Induced pluripotent stem cells (iPSCs) organ-on-chip (OOC) technologies possess suitable characteristics generation physiologically relevant in vitro allowing developmental studies, modeling, toxicological screening. Importantly, these platforms represent potential alternatives animal testing, according 3Rs (replace, reduce, refine) principle, hold promise identification approval new chemicals under European REACH (registration, evaluation, authorization restriction chemicals) framework. As such, review aims summarize recent progress made iPSC- OOC-based models. A general overview present applications models presented, followed summary used protocols generate different cell types from iPSCs. Lastly, developed iPSC-based are discussed.

Language: Английский

Citations

25
Insights on Three Dimensional Organoid Studies for Stem Cell Therapy in Regenerative Medicine DOI Creative Commons
Precious Earldom Mulaudzi, Heidi Abrahamse, Anine Crous

et al.

Stem Cell Reviews and Reports, Journal Year: 2023, Volume and Issue: 20(2), P. 509 - 523

Published: Dec. 14, 2023

Regenerative medicine has developed as a promising discipline that utilizes stem cells to address limitations in traditional therapies, using innovative techniques restore and repair damaged organs tissues. One such technique is the generation of three-dimensional (3D) organoids cell therapy. Organoids are 3D constructs resemble specific organs' structural functional characteristics generated from or tissue-specific progenitor cells. The use advantageous comparison two-dimensional (2D) culture by bridging gap between vivo vitro research. This review aims provide an overview advancements made towards regenerative generate organoids, explore used generating their applications finally elucidate challenges future directions organoids.

Language: Английский

Citations

10
Inhibitors of the Elastase LasB for the Treatment of Pseudomonas aeruginosa Lung Infections DOI Creative Commons
Jelena Konstantinović, Andreas M. Kany, Alaa Alhayek

et al.

ACS Central Science, Journal Year: 2023, Volume and Issue: 9(12), P. 2205 - 2215

Published: Oct. 27, 2023

Infections caused by the Gram-negative pathogen Pseudomonas aeruginosa are emerging worldwide as a major threat to human health. Conventional antibiotic monotherapy suffers from rapid resistance development, underlining urgent need for novel treatment concepts. Here, we report on nontraditional approach combat P. aeruginosa-derived infections targeting its main virulence factor, elastase LasB. We discovered new chemical class of phosphonates with an outstanding in vitro ADMET and PK profile, auspicious activity both vivo. established mode action through cocrystal structure our lead compound LasB several ex vivo models. The proof concept combination pathoblocker levofloxacin murine neutropenic lung infection model reduction protein levels blood target engagement demonstrate great potential use adjunctive humans.

Language: Английский

Citations

9
Development of a Human Intestinal Organoid Model for In Vitro Studies on Gut Inflammation and Fibrosis DOI Creative Commons
Leonidas Kandilogiannakis, Eirini Filidou, Ioannis Drygiannakis

et al.

Stem Cells International, Journal Year: 2021, Volume and Issue: 2021, P. 1 - 14

Published: July 27, 2021

Inflammatory Bowel Diseases (IBDs) are characterized by chronic intestinal inflammation and fibrosis, the latter being predominant denominator for long-term complications. Epithelial mesenchymal 2D cultures highly utilized in vitro models preclinical evaluation of anti-inflammatory antifibrotic therapies. More recently, human organoids (HIOs), a new 3D model derived from pluripotent stem cells, have advantage to closely resemble architecture mucosa. However, appropriate timing study inflammatory fibrotic responses, during HIO development, has not been adequately investigated. We developed HIOs embryonic cell line, H1, examined expression markers their maturation process. also investigated effect stimuli on immunological mediators. Serial extracellular matrix (ECM) revealed that an component, which gradually declines through culture passages. Specifically, CD90, collagen type I, III, fibronectin were expressed early passages but diminished late The proinflammatory cytokines IL-1α TNF-α induced mRNA fibronectin, types I tissue factor (TF), alpha-smooth muscle actin (α-SMA) primarily Similarly, elicited strong protein (CXCL10) epithelial (CXCL1, CCL2, CXCL8, CCL20) chemokine responses In contrast, tight junction components, CLDN1 JAMA, responded stimulation independently passage. Our findings indicate this contains functional passages, underline significance cells’ fitness responses. Therefore, we propose is suitable epithelial-mesenchymal interactions when component active.

Language: Английский

Citations

23
Stem cells for organoids DOI Creative Commons
Shutong Qian, Jiayi Mao, Zhimo Liu

et al.

Smart Medicine, Journal Year: 2022, Volume and Issue: 1(1)

Published: Dec. 1, 2022

Abstract Organoids are three‐dimensional (3D) cell culture systems that simulate the structures and functions of organs, involving applications in disease modeling, drug screening, cellular developmental biology. The material matrix organoids can provide a 3D environment for stem cells to differentiate into different types continuously self‐renew, thereby realizing vitro which has received extensive attention recent years. However, some challenges still exist organoids, including low maturity, high heterogeneity, lack spatiotemporal regulation. Therefore, this review, we summarized culturing protocols various cell‐derived proposed insightful thoughts engineering view current shortcomings, achieve further application clinical translation engineered organoid research.

Language: Английский

Citations

16