Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease that is characterized by progressive airflow limitation, a high prevalence, and a high mortality rate. However, the specific mechanisms remain unclear, partly due to the lack of robust data from in vitro experimental models and animal models that do not adequately represent the structure and pathophysiology of the human lung. The recent advancement of lung organoid culture systems has facilitated new avenues for the investigation of COPD. Lung organoids are in vitro models derived from adult stem cells, human pluripotent stem cells, or embryonic stem cells, established through three-dimensional culture. They exhibit a high degree of homology and genetic consistency with human tissues and can better mimic human lungs in terms of function and structure compared to other traditional models. This review will summarise the generation process of lung organoids from different cell sources and their application in COPD research, and provide suggestions for future research directions.
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http://dx.doi.org/10.1186/s12931-025-03138-4 | DOI Listing |
Cells
February 2025
Institute of Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany.
Cellular metabolism must adapt rapidly to environmental alterations and adjust nutrient uptake. Low glucose availability activates the AMP-dependent kinase (AMPK) pathway. We demonstrate that activation of AMPK or the downstream Unc-51-like autophagy-activating kinase (ULK1) inhibits receptor-mediated endocytosis.
View Article and Find Full Text PDFStem Cell Res Ther
March 2025
Shenzhen Children's Hospital, Shenzhen, 518038, China.
Background: Pulmonary fibrosis models play crucial roles in research of pulmonary fibrosis and anti-fibrosis drug screening. Despite the establishment of several pulmonary fibrosis models including lung fibrosis animals, stem cell differentiation, pulmospheres and so on, the one that mimic the personalized native lung lacks.
Methods: We here developed a lung organoid-based fibrosis (LOF) model from native lung tissue, and the potential of the LOFs for the sensitivity test of anti-fibrotic drugs was evaluated.
J Cell Sci
March 2025
Epithelial Cell Biology in ENT Research Group, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Regeneration of the airway epithelium restores barrier function and mucociliary clearance following lung injury and infection. The mechanisms regulating the proliferation and differentiation of tissue-resident airway basal stem cells remain incompletely understood. To identify compounds that promote human airway basal cell proliferation, we performed phenotype-based compound screening of 1,429 compounds (from the ENZO and Prestwick Chemical libraries) in 384-well format using primary cells transduced with lentiviral luciferase.
View Article and Find Full Text PDFNat Rev Genet
March 2025
Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Deciphering metastatic processes is crucial for understanding cancer progression and potential treatment options. Genetic studies of model systems engineered to mimic metastatic disease, including organoids, genetically engineered mice and human cell lines, have had an important role in shaping our understanding of the metastatic cascade and how it can be manipulated. More recently, advances in high-throughput sequencing have enabled human metastases to be studied at single-cell and single-nucleotide resolution, providing insights into metastatic evolution and phenotypes of both cancer cells and immune cells.
View Article and Find Full Text PDFBiol Methods Protoc
February 2025
Hangzhou Cancer Institute, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310002, China.
Patient-derived tumor organoids (PDOs) hold immense potential for personalized drug sensitivity testing, but accurate efficacy determination is crucial for clinical translation. This study investigated factors influencing the accuracy and reproducibility of drug sensitivity measurements in PDOs, focusing on half-maximal-inhibitory-concentration (IC50) calculation methods, drug concentration numbers, and plate types. PDOs were established from six primary cancer tissues, including two cervical resections, one lung biopsy, one lung pleural effusion, one breast biopsy, and one gastric resection.
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