Immune Cells Can Overcome Culture Shock

A team of scientists from Dresden and Marseille report that they have grown macrophages under laboratory conditions for an extended period of time that, when transferred back into the body, functioned normally and were indistinguishable from the cells that never left the tissue.

Macrophages are immune cells crucial for immune response, tissue repair, and the removal of cancer cells. Scientists have long considered them promising candidates for living therapeutics, but the inability to grow large numbers in laboratory cultures without impacting their functions has remained so elusive some questioned whether it was even possible. Essentially, when removed from their natural environment, put in a plastic dish, and submerged in artificial nutrient solutions, such cells experience a literal “culture shock,” and lose some of their original functions.

Prof. Michael Sieweke, Humboldt Professor at the TU Dresden, and his team at the Center for Regenerative Therapies Dresden (CRTD) at TU Dresden and the Center of Immunology of Marseille Luminy (CNRS, INSERM, Aix-Marseille University) managed to grow mouse lung macrophages under laboratory conditions over several months, achieving large numbers.  “We wanted to know exactly how the cells change in prolonged cell culture and whether these changes are permanent or not,” Sieweke says. 

Although the look and general characteristics of the cells 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 gene pattern in the cells cultured in the laboratory showed substantial differences to their counterparts from the lung. “This was to be expected,” Sieweke says. “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 3,000 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 who 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. 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,” says coauthor Clara Busch.

The ability to shuttle the macrophages between the cell culture and their natural environment shows great potential for future macrophage-based cell therapies. The 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 setup could be used to treat cancer, fibrotic disease, or infections similar to COVID-19 in the lung and eventually in other organs.

The study was published in the journal Nature Immunology.