3Rs prize runner up Dr György Fejer, from Plymouth University, speaks to the NC3Rs about how his highly commended work with macrophage cells has the potential to reduce the number of mice used in infectious disease research.
The expert panel judging entries to this year’s NC3Rs 3Rs Prize selected Dr Fejer’s work for commendation because of the positive step his research can make towards reducing animal use in the study of infection and immunity. The work will provide a powerful new tool to study inflammatory disease mechanisms.
The highly commended paper, published in Proceedings of the National Academy of Sciences, describes for the first time a method to successfully grow primary, untransformed macrophages – a particular type of immune cell – in the laboratory. Macrophage cells are part of the body’s first line of defence against various pathogens. Studies using these cells are important for improving our understanding of how the body fights infection and the onset of allergy, diabetes and cancer.
However, macrophage studies have historically used cells derived from the bone marrow of rodents. It’s estimated that over half a million rodents have been used, in the time period since 2012 alone, to provide macrophage cells for infectious disease research. Identifying the need for improvement, Dr Fejer set about finding an alternative to obtaining rodent bone marrow-derived cells that would allow self-renewing cell lines to grow without chemical, genetic or viral intervention.
Until now, advances in the understanding of macrophage biology have been hindered by the difficulty to obtain primary tissue macrophages in sufficient numbers and purity. Importantly, Dr Fejer’s self-renewing cells have the potential to become a more readily available source of macrophages for these types of studies.
There are several subsets of macrophages with different roles and the macrophages obtained by Dr Fejer’s method are very similar to lung alveolar macrophages, cells that play an important role in lung infections and asthma. He estimates that typically only 300,000 lung alveolar macrophage cells can be harvested from one mouse, which makes research involving these cells very difficult.
“In contrast, with my method you can get 30 million cells from a single tissue culture dish, which is already a hundred times more than what you can get from an animal. This work allows detailed biochemical analysis of macrophage function and also saves the lives of many experimental animals,” he explains.
Dr Fejer told the NC3Rs that, “many of these animals can be replaced by my method” going on to describe the potential impact on animal use as “very significant.”
There are other advantages too. “A transformed cell line has a genetic background which is not stable and my cell is a primary cell so we don’t have this disadvantage, we can make it from very different genetic backgrounds so we can use transgenic animals or knockout animals to study special gene functions,” he explains.
The cell line is a good model for lung alveolar macrophages, as the cells display similar immune characteristics. The use of the new macrophage cell line model in medical research has already led to new insights into infectious lung disease. This new system is also expected to be useful in the search for new drugs against important lung diseases, such as infectious inflammation and asthma.
Dr Fejer hopes the prize will add credibility to the work done so far and will help to demonstrate that it can be further improved.
Listen to the podcast to hear more about the research in Dr Fejer’s own words.
Fejer, G., Wegner, M., Gyory, I., Cohen, I., Engelhard, P., Voronov, E., Manke, T., Ruzsics, Z., Dolken, L., Prazeres da Costa, O., Branzk, N., Huber, M., Prasse, A., Schneider, R., Apte, R., Galanos, C., & Freudenberg, M. (2013). Nontransformed, GM-CSF-dependent macrophage lines are a unique model to study tissue macrophage functions Proceedings of the National Academy of Sciences, 110 (24) DOI: 10.1073/pnas.1302877110