Following infections of lung cells through various pathogens in the culture dish: this is the goal of a new joint project of two Helmholtz research groups. The scientists are attempting to reconstruct lung cells from mice in a stable in vitro model, in order to conduct research on the intrusion of pathogens such as viruses and bacteria and to test new active pharmaceutical ingredients. The project, in which scientists from the Helmholtz Centre for Infection Research (HZI) and their Saarbrücken branch office, the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), are participating, has the potential to replace numerous animal experiments in the future.
The “Centre for the Documentation and Evaluation of Alternatives to Animal Experiments (ZEBET)” at the Federal Institute for Risk Assessment (BfR) is now funding the project “Conditional Immortalization of Alveolar Epithelia Cells (CILIA)” for the duration of three years.
“It is our plan to immortalize cells from the deep lung of mice and to establish them as a model”, says Dr. Nicole Daum from HIPS. “With these alveolar epithelia cells, we can then for example examine how influenza viruses cross the pulmonary barrier.” In the department “Drug Delivery”, the scientists under the leadership of Professor Claus-Michael Lehr are conducting research that involves the characteristics of biological barriers such as lung, intestinal tract and skin. “We could also test new active ingredients on permanent lung cells, since the model represents a facsimile of the mouse lung, enabling in part a replacement of experiments on animals”, Daum explains. So that a drug can reach its place of action, it must be able to cross the tissue barrier.
Immortalizing cells and stimulating them to multiply is a procedure established for other cell types. First of all, the researchers infect the cells with viruses into which they have inserted certain genes. The viruses then do the rest of the work: They introduce the genes in a stable manner into the genetic material of the cells – the activity of these genes motivates the cell to split and multiply. Up until now however, this procedure with epithelial cells of the pulmonary alveoli, always led to the loss of barrier characteristics. Examinations on living animals have therefore always been unavoidable. The working group of Dr. Dagmar Wirth at HZI has nevertheless developed a procedure with which cells, despite the immortality, continue to retain their characteristic features.
“With another cell type, we have succeeded in stimulating controlled growth, without having to change the characteristics of the cell”, says Dagmar Wirth. The special thing about this model is: In addition to the gene for on-going proliferation, there is also a molecular on- and off-switch. “We stimulate cell division only when we need to. Now we would also like to install such a switch into the lung epithelial cells using an appropriate gene for division, enabling the cells to retain their characteristics of a biological barrier over the long term.” The cells must however be able to, despite the newly introduced genes, form a tight and if possible impermeable layer. If this is successful, it will be possible to implement them for various examinations instead of living mice. Over the long term, it would be a further step towards the “artificial lung” in the cell culture.
Helmholtz Centre for Infection Research:
The Helmholtz Centre for Infection Research contributes to the achievement of the goals of the Helmholtz Association of German Research Centres and to the successful implementation of the research strategy of the German Federal Government. The HZI focuses on the programme "Infection and Immunity". The goal of the programme is to solve the challenges in infection research and make a contribution to public health with new strategies for the prevention and therapy of infectious diseases.
Helmholtz Institute for Pharmaceutical Research Saarland:
The Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) is a branch office of the Helmholtz Centre for Infection Research (HZI) in Braunschweig and was founded together with the Saarland University in 2009. Where do new sustainable active ingredients against widespread infections come from, how can they be optimized for the application to humans and how are they delivered efficiently to the target site? The scientists at HIPS are searching for answers to these questions by deploying highly modern methods of pharmaceutical sciences.
