The comparison between the animal and human body in preclinical research is still hampered.
Despite of data and acquired knowledge of several studies, differences of physiological behaviour were inclined towards using animal models remain as the standard in preclinical studies, the need of alternative test models is still in demand. Especially because human airway differs a lot to rodent’s airway.
My work is based on the development of human 3D bronchial epithelium models to provide a test matrix for further studies as infection or use of new therapeutical treatments. My work presented a 3D bronchial tissue based on primary human epithelial cells and embedded primary human lung fibroblast in a collagen matrix. It formed a 3D compartment and contained all characteristics of a bronchial epithelium and presented a great comparison to naïve lung tissue, based on proof of histology by detecting ciliated cells, goblet cells with high mucus production, basal cell monolayer and even measured cilia movement. Nevertheless, the model with a self-assembled extracellular matrix and vascularized system provides an even more complex setting, first trails were recognized. The 3D model offered a great basic setup and enables more complex improvements, as well as implementing immune cells for future projects.
The work exhibited ability to infect the in vitro model with Influenza A virus and showed innate
immune responses of host cells. Virus inhibiting effects of the neuraminidase inhibitor Zanamivir were measured at gene and protein level. Even new therapeutical options were tested as Qßcapsid.
In vivo like properties challenged drug delivery and provided a realistic setting. In the study I tested novel delivery systems as degradable nanogels. I showed successful delivery of charged and noncharged nanogels with etanercept. The hypothesize worked, that disulphide-containing biodegradable nanogels were able to penetrate mucus glycoproteins, to approach epithelial cellsby passing through thick mucus layers. Other particles charged with Curcumin were tested. Also, lipid nanoparticles to transfect epithelial cells, to direct to new fields of genetical therapies. The study presented Cystic Fibrosis (CF) model based on CF patient’s bronchial epithelial cells. New approaches of genetical therapy can be tested on CF model.
The in vitro bronchial epithelium model enables to study infections, smart delivery systems and novel therapies in in vivo like environment.
XVIII, 179 Seiten
in vitro model
bronchial epithelial 3D model
500 Naturwissenschaften und Mathematik::500 Naturwissenschaften::500 Naturwissenschaften und Mathematik
Development of a 3D in vitro model to study lung pathophysiology
Die Entwicklung eines 3D in vitro Models zum Studieren der Pathophysiologie der Lunge
Biologie, Chemie, Pharmazie