Un nouvel angle d'approche dans la recherche sur la décompression
Les chercheurs du laboratoire Shields de l'université du Colorado à Boulder, dirigés par Wyatt Shields, professeur adjoint de génie chimique et biologique, étudient comment les microparticules artificielles, spécialement conçues pour la biomédecine, peuvent être utilisées dans des domaines tels que la biodétection, où elles se lient à certaines molécules ou cellules pour permettre l'administration de médicaments et la détection de conditions biologiques.
Shields and third-year graduate student Abby Harrell are using lung-on-a-chip devices, which offer a noninvasive way to investigate how the immune system responds to decompression sickness (DCS). They use microfluidic devices that mimic the structure of the lung’s alveolar space and microvasculature and study how immune cells react to changes in pressure and dissolved gases. Their goal is to identify potential biomarkers for DCS and explore new treatment options for DCS in a controlled lab environment.
Comment l'ingénierie et l'immunologie vous ont-elles amené à étudier l'ADD ?
Shields: My lab focuses on engineering particle systems for biomedicine. We look at applications such as biosensing and drug delivery. We’ve recently become particularly interested in how these particles interact with immune cells — specifically, how immune cells can aid the transport and function of these particles. We discovered that particles significantly impact immune cells, which led us to explore the immune system’s incredible adaptability and complexity.
About two and a half years ago we started diving into DCS and realized there is still a lot we don’t understand about its causes. We are trying to determine if the immune system plays a bigger role in DCS than we initially thought. The more we learned, the more we realized how much the immune system is involved in the condition.
Harrell: When Wyatt’s DCS project got funding through the Office of Naval Research, I was starting my first year of grad school. I was always interested in immunology and immuno-engineering. Wyatt presented this project, and I was drawn to the idea of combining traditional chemical and biological engineering with a lung-on-a-chip device. It was a direction I hadn’t expected for my PhD, but the focus on DCS and its direct relevance to divers made it compelling.
Qu'est-ce qu'un dispositif de poumon sur puce ?
Harrell: Il s'agit d'un modèle de microfluidique qui reproduit les composants des poumons, en particulier l'espace alvéolaire. Il comporte deux canaux : le canal supérieur qui imite le compartiment aérien et le canal inférieur qui représente la microvascularisation. Cette configuration nous permet d'étudier la façon dont les gaz se dissolvent dans le sang lorsque la pression augmente, ce qui se produit chez un plongeur.
It also introduces elements of lung physiology, such as gas exchange and blood flow in the alveolar space, that aren’t typically in traditional models. We can infuse whole blood, including immune cells, into the bottom channel of the chip and observe how those immune cells react to pressure changes and dissolved gases, all without using animals or human models.
Shields: We get excited as engineers to approach a problem from a different angle, so we were drawn to the lung-on-a-chip design. One key advantage of using this system is that it’s based on human biology, unlike animal models. While animal studies are invaluable and provide insights into the immune system, there’s often a gap when applying those findings directly to humans. That’s why we’re trying to use human cells for a more accurate understanding. Traditionally, human cells are studied in vitro, which means placing them in a petri dish and exposing them to conditions that mimic diving but don’t reflect the human body’s complex biology.
The lung-on-a-chip system mimics the lung structure, particularly where air comes in and the layers of cells that cover the air sacs and the blood vessels just beneath them. This setup lets us study how gases are exchanged between these layers. As Abby mentioned, we see immune responses in the blood that we wouldn’t see in a traditional petri dish model.
We’ve discovered that when we expose the lung-on-a-chip device to hyperbaric conditions, the responses differ dramatically from what we see in isolated cells. This observation suggests that the lung’s full, intact physiology is crucial to understanding what happens during DCS, and that’s why we think this model is so important.
The lung-on-a-chip allows us to address specific questions that are difficult to explore in human studies, which often need extensive ethical approvals. Since we’re working with a controlled device, we can test drugs and experiment with different strategies more freely.
Comment le dispositif est-il développé ?
Shields: J'ai une formation d'ingénieur et j'ai mis à profit mon expérience postdoctorale à l'Institut Wyss de Harvard, où le poumon sur puce a été développé à l'origine. Nous avons réalisé que nous pouvions tirer parti de cette technologie, ce qui nous a permis d'expérimenter avec des variables et de créer des modèles plus réalistes.
One of the key reasons we were excited about this project was because microphysiological systems (commonly referred to as organ-on-a-chip technologies), particularly the lung model, require a deep understanding of bioengineering principles. It’s not just about creating the device but also about managing the flow of cells, blood, and other fluids to simulate real physiological conditions. Engineering expertise ensures we mimic lung structure and function so the models work.
Un autre aspect passionnant de cette technologie, en particulier dans le contexte de l'ADD, est que la recherche utilisant des modèles d'organes sur puce n'en est qu'à ses débuts. Les modèles d'organes sur puce ne sont pas destinés à remplacer les études sur les animaux, mais plutôt à les compléter. Ils constituent une plateforme importante pour étudier les maladies dans un environnement plus contrôlé avant de passer aux modèles animaux ou aux essais cliniques.
Applying this model to DCS is particularly interesting, as we can explore this condition with a new, cutting-edge technology that hasn’t been widely used in this context. It’s an exciting opportunity to advance our understanding in a novel way.
Comment se déroule le processus de test?
Harrell: We built a custom chamber a couple of years ago that lets us control the pressure and decompression stages. We place chips in the hyperbaric chamber for about an hour to simulate recreational dive conditions and adjust the pressure profile depending on the scenario we’re studying.
After pressurizing and decompressing the system, we remove the chips and measure the immune responses. Our initial experiments focused on innate immune cells, which are the body’s first responders to stress. We use various assays to examine cellular phenotyping, looking at markers that tell us if the immune cells are in an inflammatory or anti-inflammatory state. We also analyze how these cells use secretions to communicate with each other.
Now we’re diving deeper into genetic pathways and mechanisms to explore why the cells respond the way they do.
Shields: As we better understand these systems’ physiology, we hope the lung-on-a-chip could help identify markers for diagnosing DCS. We could potentially identify inter- and intra-individual biomarkers that indicate DCS risk levels by looking at genetic and molecular mechanisms.
Si nous identifions ces marqueurs, nous pourrions tester des médicaments qui inhibent ou favorisent certaines fonctions avant de plonger. Grâce au poumon sur puce, nous pourrions tester facilement et rapidement ces médicaments en laboratoire sans avoir besoin de sujets humains, ce qui donne à cette technologie un énorme avantage pour ce type de recherche.
La Food and Drug Administration (FDA) aux États-Unis ne considère pas encore les études sur les organes sur puce comme un élément d'aide à l'approbation clinique, mais des discussions avec des représentants de la FDA suggèrent qu'ils travaillent à la normalisation des études sur les organes sur puce entre les laboratoires et à l'intégration de ces données dans le processus réglementaire des essais cliniques.
Prévoyez-vous d'utiliser d'autres organes sur puce dans le cadre de vos recherches ?
Shields: While we haven’t planned to incorporate other organ models into this specific project, there’s a growing interest in connecting multiple organ-on-a-chip devices. Linking heart, lung, and brain models could potentially offer a more comprehensive view of how responses move through the body.
These technologies are promising, but they’re not without challenges. Building and running them requires a lot of preparation and is quite expensive compared to traditional animal models. The chips also don’t replicate the full complexity of an entire organism.
We’re focused on the lungs for now because of their role in gas exchange and how pressure and dissolved gases affect them during diving. The lung model seemed like the best place to start, but if our data points us in another direction, we will happily consider exploring other organs.
En savoir plus
Découvrez Wyatt Shield et ses recherches dans cette vidéo.
© Alert Diver – Q1 2025