Researchers at Texas Biomedical Research Institute report they have created a new cell culture model for human alveolar macrophages in the lab. The model was developed to improve research for lung inflammatory diseases and may lead to the development of new potential therapies.

The findings are published in mBio in an article titled, “ A new tractable method for generating human alveolar macrophage-like cells in vitro to study lung inflammatory processes and diseases.”

“Alveolar macrophages (AMs) are unique lung resident cells that contact airborne pathogens and environmental particulates,” wrote the researchers. “The contribution of human AMs (HAMs) to pulmonary diseases remains poorly understood due to the difficulty in accessing them from human donors and their rapid phenotypic change during in vitro culture. Thus, there remains an unmet need for cost-effective methods for generating and/or differentiating primary cells into a HAM phenotype, particularly important for translational and clinical studies. We developed cell culture conditions that mimic the lung alveolar environment in humans using lung lipids, that is, Infasurf (calfactant, natural bovine surfactant) and lung-associated cytokines (granulocyte macrophage colony-stimulating factor, transforming growth factor-β, and interleukin 10) that facilitate the conversion of blood-obtained monocytes to an AM-like (AML) phenotype and function in tissue culture.”

“It is critical to study tissue-specific cells to better understand mechanisms of health and disease, and to screen potential new therapies,” said Texas Biomed professor Larry Schlesinger, MD, and senior author of the paper.

Human alveolar macrophages have been challenging to study because they reside deep in the lungs and are hard to access. The new model starts with a blood draw. White blood cells are isolated and placed in Teflon jars with specialized cell culture components. Surfactant is added along with three different cytokine proteins, which are usually found in the alveolar lining fluid.

“We call it the magic cocktail,” explained Susanta Pahari, PhD, a postdoctoral researcher at Texas Biomed and first author of the paper. “We are mimicking the alveolar environment in cell culture. It makes the cells think they are in the lungs.”

Within six days, the cells differentiate, or transform, into alveolar macrophage-like cells. The generated cells are 94% genetically similar to human alveolar macrophages collected from lung washes. The Texas Biomed team confirmed the model can be used to investigate TB and COVID-19; the cells readily take up the pathogens.

“It is very rewarding to develop something that can help the research community,” said Pahari. “We’ve already received numerous emails across the globe requesting macrophage development protocols. We are now looking into developing a kit that we can provide to make it even easier for others to replicate what we have done.”

“I am excited to see the full potential of the alveolar macrophage-like cells and if they can be integrated into next-generation lung organoids,” Schlesinger added.

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