“…This model resulted in the acquisition of EMT markers by the cancer cell line, while treatment with an established chemotherapeutic showed a decrease in viability. [ 77 ] Organoids have also proven to be a very powerful tool for multicellular models of cancer. Primary tumor‐derived organoids containing lung cancer cells alongside both fibroblasts and inflammatory cells showed a higher resistance to chemotherapeutics than did primary cells grown on tissue‐culture plastic, highlighting again the importance of environmental context in predicting cellular responses to treatment.…”
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 has been 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 reveal 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 study of carcinogenesis and chemoprevention strategies.This article is protected by copyright. All rights reserved
“…This model resulted in the acquisition of EMT markers by the cancer cell line, while treatment with an established chemotherapeutic showed a decrease in viability. [ 77 ] Organoids have also proven to be a very powerful tool for multicellular models of cancer. Primary tumor‐derived organoids containing lung cancer cells alongside both fibroblasts and inflammatory cells showed a higher resistance to chemotherapeutics than did primary cells grown on tissue‐culture plastic, highlighting again the importance of environmental context in predicting cellular responses to treatment.…”
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 has been 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 reveal 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 study of carcinogenesis and chemoprevention strategies.This article is protected by copyright. All rights reserved
“…For example, a study that bioprinted a mixture of cancer cell and fibroblast lines into a 3D hydrogel exposed cells in this culture system to CSE. This model resulted in the acquisition of EMT markers by the cancer cell line, while treatment with an established chemotherapeutic showed a decrease in viability 86 . Organoids have also proven to be a very powerful tool for multicellular models of cancer.…”
Lung cancer is the leading global cause of cancer-related deaths. Although smoking cessation is the best preventive action, nearly 50% of all lung cancer diagnoses occur in people who have already quit smoking. Research into treatment options for these high-risk patients has been constrained to rodent models of chemical carcinogenesis, which are time-consuming, expensive, and require large numbers of animals. Here we show that embedding precision-cut lung slices within an engineered hydrogel and exposing this tissue to a carcinogen from cigarette smoke creates an in vitro model of lung cancer premalignancy. Hydrogel formulations were selected to promote early lung cancer cellular phenotypes and extend PCLS viability up to six weeks. In this study, hydrogel-embedded lung slices were exposed to the cigarette smoke derived carcinogen vinyl carbamate, which induces adenocarcinoma in mice. At six weeks, analysis of proliferation, gene expression, histology, tissue stiffness, and cellular content revealed that vinyl carbamate induced the formation of premalignant lesions with a mixed adenoma/squamous phenotype. Two putative chemoprevention agents were able to freely diffuse through the hydrogel and induce tissue-level changes. The design parameters selected using murine tissue were validated with hydrogel-embedded human PCLS and results showed increased proliferation and premalignant lesion gene expression patterns. This tissue-engineered model of human lung cancer premalignancy is the starting point for more sophisticated ex vivo models and a foundation for the study of carcinogenesis and chemoprevention strategies.
“…Creation of models allowed e.g. , analysis of DNA phenotype changes during metastasis [52] , study on lung cancer impact on muscle cachexia [53] , drug-dose testing [ 54 , 55 ] or mimicking tumor growth in vitro [56] . The researchers working on 3D bioprinting of lung cancer models claim that this method is faster, has lower technical and personal entry thresholds, and has higher success rates in comparison to currently used tumor organoid culture methods ( Fig.…”
Section: D Bioprinted Models Of the Highly Malignant Cancersmentioning
confidence: 99%
“…The researchers working on 3D bioprinting of lung cancer models claim that this method is faster, has lower technical and personal entry thresholds, and has higher success rates in comparison to currently used tumor organoid culture methods ( Fig. 3 ) [ 55 , 57 ]. Fig.…”
Section: D Bioprinted Models Of the Highly Malignant Cancersmentioning
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