Evaluation of 3D cell culture systems for host-pathogen interaction studies

Marrazzo, Pasquale (2015) Evaluation of 3D cell culture systems for host-pathogen interaction studies , [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Biologia cellulare e molecolare, 27 Ciclo. DOI 10.6092/unibo/amsdottorato/7010.
Documenti full-text disponibili:
Documento PDF (English) - Richiede un lettore di PDF come Xpdf o Adobe Acrobat Reader
Download (4MB) | Anteprima


Traditional cell culture models have limitations in extrapolating functional mechanisms that underlie strategies of microbial virulence. Indeed during the infection the pathogens adapt to different tissue-specific environmental factors. The development of in vitro models resembling human tissue physiology might allow the replacement of inaccurate or aberrant animal models. Three-dimensional (3D) cell culture systems are more reliable and more predictive models that can be used for the meaningful dissection of host–pathogen interactions. The lung and gut mucosae often represent the first site of exposure to pathogens and provide a physical barrier against their entry. Within this context, the tracheobronchial and small intestine tract were modelled by tissue engineering approach. The main work was focused on the development and the extensive characterization of a human organotypic airway model, based on a mechanically supported co-culture of normal primary cells. The regained morphological features, the retrieved environmental factors and the presence of specific epithelial subsets resembled the native tissue organization. In addition, the respiratory model enabled the modular insertion of interesting cell types, such as innate immune cells or multipotent stromal cells, showing a functional ability to release pertinent cytokines differentially. Furthermore this model responded imitating known events occurring during the infection by Non-typeable H. influenzae. Epithelial organoid models, mimicking the small intestine tract, were used for a different explorative analysis of tissue-toxicity. Further experiments led to detection of a cell population targeted by C. difficile Toxin A and suggested a role in the impairment of the epithelial homeostasis by the bacterial virulence machinery. The described cell-centered strategy can afford critical insights in the evaluation of the host defence and pathogenic mechanisms. The application of these two models may provide an informing step that more coherently defines relevant molecular interactions happening during the infection.

Tipologia del documento
Tesi di dottorato
Marrazzo, Pasquale
Dottorato di ricerca
Scuola di dottorato
Scienze biologiche, biomediche e biotecnologiche
Settore disciplinare
Settore concorsuale
Parole chiave
3D cell culture; airway model; organoid; host-pathogen interaction; in vitro model; HBEC; NHBE; organotypic;
Data di discussione
10 Aprile 2015

Altri metadati

Statistica sui download

Gestione del documento: Visualizza la tesi