Konditionale Immortalisierung alveolarer Epithelzellen zur Etablierung infektionsrelevanter in vitro Modelle der Lunge/ Conditional Immortalization of Alveolar Epithelial Cells

The air-blood interface in the lung represents the most important barrier for inhaled drug components, xenobiotics and infectious particles. In this process, the pulmonary absorption of components mediated by the alveolar epithelium is a crucial step. Thereby, animal experiments are still indispensable for the identification of novel drugs and to answer numerous biological questions. The aim of the project “CILIA” (conditional immortalization of alveolar epithelial cells) is the development of novel expandable alveolar type I and II cell lines, which are based on conditionally immortalized alveolar cells of different mouse mutants. The immortalization is performed by lentiviral vectors carrying well-characterized expansion and proliferation genes that do not alter the typical cell physiology and function. These systems will then be utilized in thoroughly characterized and optimized in vitro models serving as surrogates for in vivo studies. Thus, animal experiments can be replaced according to the 3R-principle (refine, reduce, replace). The established alveolar cell lines will help elucidating infection pathways of different pathogens (e.g. influenza) across the respiratory tract. Furthermore, they will serve as powerful tool in the development of antiinfectives to treat such diseases. Beyond this, such cell models are the basis for the development of consistent and complex 3D in vitro systems without any limitation in numbers and importantly with the highest possible reproducibility.


Funding Agency

BMBF - Federal Ministry of Education and Research