3D model of the infant lung to treat RSV bronchiolitis

At the Institute of Child Health at Great Ormond Street Children’s Hospital, Dr Claire Smith and her team are developing a new 3D model of the infant lung to accurately mimic the conditions of RSV bronchiolitis – a life-threatening lung infection.

 

 

The problem

Every year 34,000 children in the UK under the age of five are hospitalised by the highly contagious respiratory syncytial virus (RSV) which is the main cause of bronchiolitis (inflammation of the small airways in the lungs).

For most children RSV is relatively mild, however some children, especially premature babies, and those under six months of age, go on to develop pneumonia and can end up spending long periods in intensive care. Some also acquire long-term health problems such as asthma.

Due to COVID-19 pandemic and lockdowns, RSV did not circulate as much as usual meaning that pregnant women have not acquired natural immunity as a result of prolonged absence of contact, which could mean a change in the severity of the infection in young children.

 

Still no treatment

There are no specific treatments to stop RSV bronchiolitis nor a preventative vaccine.

Progress has been hampered by an inadequate understanding of the development of this condition. 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 to study this virus, but we know that this is not the best way. Mice are often more resistant to the virus than humans, and their lungs differ in important ways.

 

“Decades of animal-based studies have failed to translate into the major breakthroughs needed to improve current respiratory treatment. Human relevant model systems are urgently required. This is because human viruses, particularly RSV, show a specificity to infect a certain type of cell found only in the human airway”.

 

The solution

At Animal Free Research UK, we are funding a project at the forefront of the human relevant revolution. At the Institute of Child Health at University College London, Dr Claire Smith and her team are developing a new 3D model of the infant lung to accurately mimic the conditions of RSV bronchiolitis, including the immune response, and to improve our understanding of the virus.

Across the three years of the project, the team will develop these ‘mini lungs’ using organ-on-a-chip technology – chips that allow the study of fluid flows like blood and air circulation systems, and air-liquid interface, mimicking what happens in the human body.

They will grow epithelial cells on a chip to mimic the structure of human lung. Epithelial cells form the covering of all body surfaces and lining. These cells serve many important functions within the lung including barrier protection, initiation of immune responses and damage repair.

This model will enable the outer layer of the human lung to be studied using patient tissue from an ethically sourced human tissue bank allowing for more accurate and translatable research into the disease mechanisms of RSV, and to build baseline data to identify potential new treatments and vaccines.

Dr Smith’s model will not only be used to screen potential drugs to treat this life-threatening lung infection, but also to eliminate the use of animals in RSV research and, potentially, in other areas of respiratory disease research.

 

Interview with Dr Claire Smith