Julia Chivu ’23
Macrophages typically dominate the immune system with broad responsibilities related to cell repair, immune response, and homeostasis. However, macrophages also have organ-specific functions embedded into their epigenetic makeup. These powerful and specialized cells may be used in various macrophage therapies that can impact both humans and animals. In spite of this astounding potential, these treatment options are not available yet since scientists have found it challenging to maintain large quantities of most types of macrophages in laboratory cultures. Thus far, only scientists from the Dresden University of Technology in Germany and Aix-Marseille University in France managed to grow large numbers of alveolar macrophages, located in lung tissues, in laboratory conditions. Therefore, the scientists from these two universities conducted an experiment to compare the function and gene expression of their lab-grown macrophages to those of their in vivo lung counterparts. The alveolar macrophages were then taken out of cell cultures to identify if they would be able to restore their epigenetic identity when transplanted back into their original environment.
Cell culture is a commonly used technique where cells are taken from their natural environment and placed onto a plastic dish containing a solid nutrient solution and incubated to allow for growth. The cells are ‘culture shocked’ into potentially adapting to new conditions in an environment containing none of their familiar necessities or natural signals. In this experiment, macrophages were removed from the lungs of female and male mice and cell cultured. After genetic analysis, the macrophages were reintroduced into the mouse lungs.
When comparing the mouse macrophages to their cultured equivalents, significant differences were observed in their functionality and genetic expression. The lab-grown macrophages had adapted to their new surroundings because their migration, cell adhesion, signaling pathways, cell proliferation, etc. were no longer similar to the mouse macrophage equivalents. On the contrary, the lab-grown macrophages placed into the lungs of mice showed very few differences compared to the macrophages already present in the lungs. The cells essentially “forgot” about their cultured conditions to thrive in their original environment. This experiment proved that long-term proliferation in a new environment does not impact the transcriptional identity of the alveolar macrophages. Future research into this field of study can allow for new drugs to be created with the help of macrophages that can ideally combat infections as well as repair damaged organs.
 S. Subramanian, et al., Long-term culture-expanded alveolar macrophages restore their full epigenetic identity after transfer in vivo. Nature Immunology 23, 458-468 (2022). doi: 10.1038/s41590-022-01146-w.
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