Cell model for the human lung

Before new drugs can be tested in animal experiments and later in clinical trials, they have to undergo a variety of laboratory tests. This involves the use of cell lines, i.e. human or animal cells of a specific tissue that can be cultivated in the laboratory. A team led by Prof. Claus-Michael Lehr from the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) has now developed a new type of human lung cell line that should enable much more accurate predictions to be made about the behaviour of active substances or drug forms in humans than previous systems. The cell line could be used, for example, in the development of active substances against SARS-CoV-2. The scientists published their results in the scientific journal Advanced Science.

The ability to grow individual human cells in the laboratory has allowed researchers since the 1950s to investigate new drug candidates in the laboratory without having to carry out tests on animals or even humans. In many cases, the cultured cells are cancer cells. This has the advantage that they are available in large numbers, as they can potentially multiply indefinitely, but also means that the cells differ significantly in many properties from healthy cells. As drug research involves investigating substances that are to be tested on animals and humans later in the development process, it is of great importance that the model systems used can predict the behaviour of a drug in the living organism as accurately as possible. This is where the work of Claus-Michael Lehr's team comes in. Lehr is head of the Department of Drug Transport via Biological Barriers at HIPS and Professor of Biopharmacy and Pharmaceutical Technology at Saarland University. The HIPS is a site of the Helmholtz Centre for Infection Research in cooperation with Saarland University.

Reducing animal experiments
Claus-Michael Lehr's group has been working for many years on the development and application of biological model systems that imitate various human organs and are therefore intended to reduce and ultimately replace animal testing. The current research work is focussing on the human lung. Based on the lung epithelial cell line „hAELVi“, which was published in 2016, the cell line „Arlo“ has now been developed as part of the work of PhD student Patrick Carius. „Arlo was created from a single hAELVi cell, which we obtained by so-called single-cell printing“, explains Dr Nicole Schneider-Daum, senior scientist from Lehr's department. „This means that all cells originate from a single hAELVi precursor cell and are therefore genetically identical.“ In the laboratory, Arlo forms a very dense cell layer that is similar to the human epithelium in the deep lung. In addition, the cell line provides very reproducible results, as it is a more uniform cell population than the predecessor. Both cell lines were artificially immortalised, i.e. they reproduce as often as desired without exhibiting undesirable cancer-like properties.

The potential field of application of Arlo is versatile: On the one hand, the cell line offers a platform for testing new active substances or nano-carriers that are to be administered as an aerosol. On the other hand, Arlo can also be used in infection models for bacterial or viral diseases. „This combination makes our development potentially a very valuable tool for the study of SARS-CoV-2 infections and agents to combat them,“ says Lehr. Our cell lines should mimic the situation in the human lung so well that we can reduce the number of animal experiments required and even replace them completely at some point. The hAELVi progenitor cell line has been commercially available for several years and is already being used in over 50 laboratories worldwide. This makes us very proud and shows that we have been able to make a valuable contribution to the international research landscape with our research. We are convinced that Arlo, which is now also commercially available, will be just as well received by the community in the coming years and can also make a valuable contribution to new developments and findings.

In its study, which involved researchers from Saarland University and Frankfurt University Hospital as well as doctors from SHG Kliniken Völklingen, the research team comprehensively characterised its new cell line and has already used it in a SARS-CoV-2 infection model. In future, Arlo will also be used in more complex model systems in which the cell line is combined with other cell types. This should make it possible to achieve results that even better reflect the actual situation in the living organism.

About the institutes:
The Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) in Saarbrücken was founded jointly by the HZI and Saarland University in 2009. The researchers here are looking in particular for new active substances against infectious diseases, optimising them for use in humans and researching how they can best be transported to their site of action in the human body. Further information can be found at www.helmholtz-hips.de

At the Helmholtz Centre for Infection Research (HZI) scientists in Braunschweig and at other locations in Germany investigate bacterial and viral infections as well as the body's defence mechanisms. As a member of the Helmholtz Association and the German Centre for Infection Research (DZIF), the HZI conducts translational research to lay the foundations for the development of novel therapies and vaccines against infectious diseases. Further information can be found at www.helmholtz-hzi.de

Notification from "LABO" dated 09 February 2023