In vitro airway models aid researchers in studying infections that affect the lungs, such as COVID-19, but models produced from primary pulmonary epithelial cells are limited to primary samples that can differ significantly between various donors’ genetic backgrounds. A research team at Newcastle University has developed a new type of airway model made from induced pluripotent stem cells (iPSCs) that propagate indefinitely, providing a large supply of cells with the genetic background of a single donor.
iPSCs are generated from adult stem cells found in fat, skin, blood and elsewhere, and can be reprogrammed to become every other cell type in the body. Newcastle researchers generated airway epithelial cells from iPSCs using a mixed population of lung progenitors by culturing them on a polyester membrane to allow the formation of a confluent monolayer, then exposing them to an air liquid interface to induce differentiation into a pseudostratified epithelial model. The researchers were able to demonstrate that the model is composed of the cell types found in the human upper airway epithelium, including functional cilated cells, and that the cells are capable of secreting mucus and being readily infected with SARS-CoV-2.
“The infected model cells also secreted cytokines at levels corresponding to the behavior of the airway epithelium in the body following SARS-CoV-2 infection,” said Lyle Armstrong, professor of stem cell sciences and corresponding author on the study, which was published in the journal STEM CELLS.
“Our protocol not only simplifies the manufacture of cellular models of the human upper airways, but it has a distinct advantage in that we have eliminated the need for primary samples that differ in genetic backgrounds,” said Armstrong. “Our next step will be to expand on this model by including immune cell components.”
The availability of a reproducible airway model created from iPSCs could greatly enhance research into SARS-CoV-2 and other respiratory viral infections, and ultimately aid in the development of therapies to fight these infections.
Photo: Lyle Armstrong, Ph.D., professor of stem cell sciences at Newcastle University, UK and corresponding author on the study. Credit: AlphaMed Press