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- W2286291292 abstract "Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide. At the moment no curative treatment is available. Thus far, lung transplantation is the only option however donor organ shortage limits its general clinical application. New therapies are desperately needed. Here, 3D ex vivo lung tissue cultures (3D-LTC) from diseased murine and human lungs were applied to study repair and remodelling in high spatio-temporal resolution. In a first step, the method of 3D-LTC generation and cultivation was optimized and improved. Cell viability and proliferation was maintained until day seven. Murine and human lung samples were examined by histology, immunofluorescence, spatio-temporal confocal live-cell-imaging, as well as gene and protein expression analyses to fully characterize the suitability of the model for signal pathway modulation. Previous reports demonstrated that Wnt/beta-catenin signal activation led to attenuation of experimental emphysema in mice [Kneidinger, et.al., 2011]. TGF-beta is another pathway involved in COPD and a lack of TGF-beta seems to be related to the emphysematous changes [Budd, et.al., 2012]. To get insight into disease underlying mechanisms the COPD-relevant signalling pathways Wnt/beta-catenin and TGF-beta were activated in 3D-LTC from COPD patients and emphysematous animals. It was demonstrated that Wnt/beta-catenin signal activation initiated epithelial repair in 3D-LTC. Moreover, Wnt/beta-catenin pathway activation and alveolar epithelial type II cell activation significantly correlated with individual disease stage suggesting that 3D-LTC from patients are suitable for individual drug validation and therapy prediction. TGF-beta signalling activation led to the production of extracellular matrix components and induced expression of transcription factors and genes involved in epithelial-to-mesenchymal transition. In conclusion, the model of 3D-LTC established in this thesis allows quantification and spatio-temporal visualization of regenerative processes in the lung. It is suitable to validate and give further mechanistical insight of Wnt/beta-catenin and TGF-beta induced lung repair and remodelling, as well as treatment response prediction to individualized therapy. Thus, the 3D-LTC model presents a superior system for preclinical drug validation." @default.
- W2286291292 created "2016-06-24" @default.
- W2286291292 creator A5022428036 @default.
- W2286291292 date "2015-07-01" @default.
- W2286291292 modified "2023-09-23" @default.
- W2286291292 title "Determination of lung regeneration using an ex vivo tissue slice model" @default.
- W2286291292 hasPublicationYear "2015" @default.
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