Macrophages can readjust to the body after cell culture

European researchers have shown that macrophages grown for long periods in laboratory conditions can restore their normal functions when introduced back into the body — even after being multiplied to large numbers. Their results have been published in the journal Nature Immunology.

Macrophages are immune cells that are present in all organs of our body, acting as tissue guardians, nurturing other cells and removing detrimental substances such as bacteria, cellular debris and even tumour cells. Macrophages have therefore been on the radar of scientists as potential living drugs to heal damaged organs, fight infections and combat cancer; this would however require the cells to be grown outside of the body in large numbers, which caused concern that laboratory conditions might make them lose their special abilities. This is because cells grown in the lab are removed from their natural environment and the physical signals that appear essential to their function, so they have to adapt to these conditions — a literal culture shock.

“We wanted to know exactly how the cells change in prolonged cell culture and whether these changes are permanent or not,” said study leader Professor Michael Sieweke.

Prof Sieweke’s team at Technische Universität (TU) Dresden and Aix-Marseille University studied mouse lung macrophages — immune cells that naturally live in the air sacs of the lung. The team managed to grow the cells under laboratory conditions over several months and in large numbers. Although their looks and general characteristics were not affected, when examined more closely, it became clear that the cells had actually acquired many changes to adapt to the new environment. The scientists compared the gene pattern in the cells cultured in the laboratory with their counterparts from the lung and saw substantial differences.

“This was to be expected,” Prof Sieweke said. “Living on a plastic surface and having all the nutrients readily available is quite different from natural conditions. The cells had to get used to it and did so by changing the status of more than 3000 genes. The question that truly interested us was whether these changes can be reversed.”

The team transferred the macrophages cultured in the lab back into their natural location in the mouse lungs. Detailed comparisons showed that the cells grown in the laboratory were indistinguishable from their equivalents that never left the lung.

“We were surprised to see that the substantial adaptations that the macrophages made to live in the laboratory have proven to be completely reversible,” said study co-author Clara Busch, from TU Dresden. “The lab-cultured macrophages had forgotten about the time they spent in the lab and fully assumed their normal function and status in the lung, oblivious of their previous culture shock.”

Although the research was performed in mice, it has promising implications for human therapies. The ability to shuttle the macrophages between the cell culture and their natural environment shows great potential for future macrophage-based cell therapies; for example, lung macrophages could be multiplied in the laboratory and experimentally tailored for battling a specific disease before being delivered to the patient’s lungs where they can immediately start to perform their function. Such a set-up could be used to treat cancer, fibrotic disease, or infections similar to COVID-19 in the lung and eventually in other organs.

Image caption: Alveolar macrophages are the immune cells that specifically live in the lung air sacs, here visible as red dots in an otherwise transparent mouse lung. Image ©Sara Gholamhosseinian Najjar and Michaela Burkon.

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