Growing a complete nasal epithelium
In the laboratory, the stem cells are grown as so-called nasal organoids. These can then be used to make human nasal epithelium that has all the different specialised cell types found in a human nose. They organise themselves in layers. The result is a complete, 3-dimensional nasal epithelium. Small hairs, cilia, grow on its surface in the same way as in a real nose.
“It’s a unique model for studying viruses that infect the airways, because it mimics the human nasal epithelium. Such studies have not been possible before, and it‘s only in the last few years that we’ve been able to start growing nasal stem cells,” says Docent Marie Hagbom.
IgA antibodies are the first defence against many viruses
Most often when we think of protection against infections, we mean antibodies of the IgG type, which are found in the blood. But there are others too. IgA antibodies are found on all mucous membranes, for example in the nose and intestines. They are part of the body’s first protection against viruses and bacteria. Should harmful microorganisms manage to penetrate this defence and spread via the blood, IgG antibodies can take over the defence.
Exploring the body's protection against viruses
The IgA antibodies get to the mucous membranes via the blood and are transported through the layers of cells in the nose. How this happens is relatively unexplored.
The LiU researchers are therefore investigating how the IgA antibodies pass through the cells in the mucous membrane of the nose and how they protect against various viruses that cause respiratory infections, such as measles, SARS-cov-2 and RS virus. This is where the cultivated human nasal epithelium will be used.
“We need to understand how the body’s IgA protection works. How are the IgA antibodies transported across the nasal epithelium? How well does the presence of IgA antibodies in the nose correlate with protection against viral infection?,” says Marie Hagbom.
Can reveal differences between individuals
Using other methods to study infection, researchers need to add various substances, enzymes, to get the virus into the cells. This is not necessary in the nasal epithelium model that Marie Hagbom uses. As the nasal epithelium has the enzymes and functions that are naturally present in the nose, scientists only have to add viruses for a natural infection to occur. The SARS-Cov-2 trials are conducted in a biosafety level 3 (out of 4) laboratory at LiU, while trials on measles and RS viruses can be conducted in lower-level labs.
One major advantage of the method is that the cells are healthy, normal human cells grown from many individuals. Since each individual, and therefore each nose organoid, is genetically unique, researchers can study individual differences.
“Just look at the COVID-19 pandemic – there’s a huge difference in how different people respond to the infection. It’s a major breakthrough that we can study how different individuals respond to the same microorganism now that we can take stem cells from different people,” says Lennart Svensson.
