Lung disease research showcased at recent Physiology Conference: Developing a novel 3D model of the human lung to study bronchiolitis
Published on August 17, 2023
Machaela Palor, our Animal Free Research UK PhD student, working with Professor Claire Smith at the Institute of Child Health at University College London, recently presented a poster at the Physiology 2023 conference in Harrogate.
She showcased her progress in developing a humanised 3D lung model or ‘mini-lung’ which accurately reflects the conditions of RSV bronchiolitis, a viral chest infection caused by the highly contagious respiratory syncytial virus (RSV).
This conference brings together physiologists at all career stages from across the globe to discuss their work, share ideas and make new connections.
Progress in tackling RSV bronchiolitis
RSV bronchiolitis is a distressing, potentially life-threatening lung infection that affects over 33 million babies and infants worldwide. There is no licensed RSV vaccine or effective anti-viral treatment available. Machaela’s goal is to help improve our understanding of the virus and in particular, how our immune system responds to it.
Progress in tackling RSV bronchiolitis has been hampered by an inadequate understanding of how the disease develops. Scientists still heavily rely on animals to research RSV despite decades of animal tests failing to bring any major breakthroughs. Generations of mice and rats continue to suffer through research into the virus, but we know that this is not the best way to study the disease as animal lungs work differently to those of people. Human viruses, particularly RSV, have a specific tendency to infect certain types of s found only in the human airway. Mice are often more resistant to the virus than people, with infected animals often showing few symptoms. A more effective human-focused model to study this disease is therefore urgently needed.
Developing ‘mini-lungs’ to investigate role of the immune system in RSV bronchiolitis
The ‘mini lungs’ that Machaela is developing are made by growing cells found in human airways. Blood and air flows are mimicked using tiny fluid and air-filled channels that can form an interface. Machaela’s research is focused on the immune system’s response to RSV bronchiolitis, when it is kicked into action during a viral lung infection.
Neutrophils are a type of immune cell involved in this immune response. These cells travel from the blood and cross cells called endothelial cells that line blood vessels. They then have to cross another layer of cells called epithelial cells within our airways. However, these neutrophils can cause more harm than good, as they travel from the blood into the airways, and can damage delicate lung tissues. This can interfere with the passage of inhaled oxygen when it travels from the lungs into the blood for transport around the body. In infants with severe RSV bronchiolitis, this rapid influx of neutrophils can cause the lining of airways to become inflamed and blocked, leading to the severe symptoms of the condition.
The route that immune cells, such as neutrophils, take when they travel towards an area of infection in the lungs. The neutrophils (shown in purple) travel from the blood into the lungs by crossing endothelial cells that line blood vessels (shown in red) and then epithelial cells that line lung tissue (shown in yellow)
Machaela is using specialised microscopes to visualise and track the movement of neutrophils within the 3D lung model during an infection.
Image showing neutrophils that have been isolated from blood and stained for visualisation under the microscope
Progress in the research project so far
Machaela’s poster showcased progress in her project so far, illustrating how her model can successfully mimic RSV disease conditions. She has used the innovative mini-lung model to:
- successfully grow airway epithelial cells (cells that line our airways)
- successfully grow endothelial cells (cells which line blood vessels lying close to airways and enable gas exchange)
- show that when epithelial cells in the airways are infected with RSV, there is more migration of neutrophils from the blood into the lungs
- identify some of the key chemicals that drive the movement and influx of neutrophils, causing the lung airway lining to become inflamed and damaged
- show that neutrophils change the way they behave by reversing their direction and migrating back into the circulation, damaging epithelial cells in the process.
The impact of this research
This cutting edge mini-lung model will not only be used to develop and screen potential life-saving drugs and treatments but will also pave the way towards eliminating the use of animals in RSV research and potentially, in other areas of respiratory disease research.
“The successful development of this model will allow us to further our understanding of what causes neutrophils to infiltrate and damage the lung during RSV infection and provide a human-relevant model that can be used for anti-viral drug discovery. Ultimately, this will support the replacement of animals in the study of human respiratory diseases and anti-viral testing.” – Machaela Palor