Hydrogel-Embedded Precision-Cut Lung Slices Model Lung Cancer Premalignancy Ex Vivo.

Autor: Blomberg R; Department of Bioengineering, University of Colorado, Denver |Anschutz, Aurora, CO, 80045, USA., Sompel K; Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA., Hauer C; Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA., Smith AJ; Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA., Peña B; Department of Bioengineering, University of Colorado, Denver |Anschutz, Aurora, CO, 80045, USA.; Cardiovascular Institute & Adult Medical Genetics, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA., Driscoll J; Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, National Jewish Health, Denver, CO, 80206, USA., Hume PS; Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.; Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, National Jewish Health, Denver, CO, 80206, USA., Merrick DT; Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA., Tennis MA; Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA., Magin CM; Department of Bioengineering, University of Colorado, Denver |Anschutz, Aurora, CO, 80045, USA.; Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.; Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2024 Feb; Vol. 13 (4), pp. e2302246. Date of Electronic Publication: 2023 Nov 27.
DOI: 10.1002/adhm.202302246
Abstrakt: Lung cancer is the leading global cause of cancer-related deaths. Although smoking cessation is the best prevention, 50% of lung cancer diagnoses occur in people who have quit smoking. Research into treatment options for high-risk patients is constrained to rodent models, which are time-consuming, expensive, and require large cohorts. Embedding precision-cut lung slices (PCLS) within an engineered hydrogel and exposing this tissue to vinyl carbamate, a carcinogen from cigarette smoke, creates an in vitro model of lung cancer premalignancy. Hydrogel formulations are selected to promote early lung cancer cellular phenotypes and extend PCLS viability to six weeks. Hydrogel-embedded PCLS are exposed to vinyl carbamate, which induces adenocarcinoma in mice. Analysis of proliferation, gene expression, histology, tissue stiffness, and cellular content after six weeks reveals that vinyl carbamate induces premalignant lesions with a mixed adenoma/squamous phenotype. Putative chemoprevention agents diffuse through the hydrogel and induce tissue-level changes. The design parameters selected using murine tissue are validated with hydrogel-embedded human PCLS and results show increased proliferation and premalignant lesion gene expression patterns. This tissue-engineered model of human lung cancer premalignancy is the foundation for more sophisticated ex vivo models that enable the study of carcinogenesis and chemoprevention strategies.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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