Air-liquid interface (ALI): innovative progress

Toxicologist Yvonne Staal (National Institute for Public Health and the Environment, RIVM) is the project leader of various studies that are using human cells to investigate the harmfulness of substances to the airways. “For example, we are investigating how cells react to a combination of substances in the air and pathogens. Through the use of human cells, we gain a better picture of how human lungs react to exposure to certain substances.”

Yvonne Staal
Beeld: RIVM
Yvonne Staal

“Air-liquid interface (ALI) is the way in which cells are cultured in order to be able to expose them to air. We do this in order to test how human lung cells react to certain substances, for example. After all, substances behave differently in air than they do in liquids,” says Staal. “In recent years, we have investigated this for various different cell models. Cell lines were used for this purpose. We also use cells from healthy lung tissue, which are left over after lung surgery and then cultivated by us. These cells are then exposed to various substances via the air.”

“For example, RIVM is conducting ALI research into the respiratory symptoms of people who live near livestock farms and for which the cause is unknown. The cell model can also be used for other research. Both biological and technical aspects are important if these experiments are to be carried out properly. For example, you also need to know how to properly expose cell models to air. It is much easier to introduce a substance into the cell culture medium than into the air, especially if it has to remain stable over a certain period of time.

“You could say that research with laboratory animals has made the world safer for rats but not necessarily for humans.”

Better estimate

According to Staal, the use of human cells rather than laboratory animals makes it possible to estimate how human lung cells will react to exposure to certain substances. “The use of laboratory animals is sometimes necessary. But if you don't have to, you shouldn't use them. The regulations for new drugs or chemicals often still prescribe animal testing. The information provided by animal procedures is different from the information that we will receive from cell models in the future. You could say that research with laboratory animals has made the world safer for rats but not necessarily for humans.”

According to Staal, we are still at the beginning of the transition to animal-free innovation. “Although there is already a lot of knowledge, its actual application to new substances also depends on how much confidence we have in the knowledge we have acquired. It’s good that we are already taking numerous steps with the use of human cell models, because this teaches us which properties are important for determining the toxicity. It also means that we may soon be using other cell models that mimic reality even more accurately. Or maybe we'll use cell models that have the exact properties that are important for determining the toxicity. In this respect, this kind of research is increasingly gaining a foothold in a more mechanical approach to toxicology, rather than putting everything in a black box and then looking at the harmful effects that occur.

“Through the use of human cells, we gain a better picture of how human lungs react to exposure to certain substances.”

European research

A great deal of European research is already being carried out into the standardisation of animal-free research using ALI models. For example, Staal’s RIVM colleagues Hedwig Braakhuis and Rob Vandebriel recently published an article and a protocol on the website of JoVE, the scientific video journal, on testing and how to standardise airway research with aerosols. 

“The current COVID-19 crisis also offers opportunities for the further development of ALI models. We can already investigate SARS-CoV-2 using the cell models we currently have. This not only gives us more insights into the possibilities of the cell models but also enables us to better determine the application possibilities. The prospect of using these kinds of in vitro models in a new way to determine toxicity makes me very enthusiastic and really inspires me to continue down this path.”