3 April 2015

Growing ‘mini-lungs’ in the fight against child mortality

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Every year, around 250,000 children worldwide die from respiratory tract infections caused by the human respiratory syncytial virus (RSV). Paediatrician Louis Bont and cell biologist Norman Sachs utilize miniature lungs developed in the Hubrecht Institute to model RSV infection and develop a vaccine. They have been awarded a Seed Money Grant by the University to initiate the project.

“Respiratory syncytial virus often causes colds in older children and adults during the winter, says Louis Bont, paediatrician at the Wilhelmina Kinderziekenhuis children’s hospital in Utrecht, part of UMC Utrecht. “Only children become really ill. The virus is the second biggest cause of child mortality in the world and the most common reason for children being admitted to hospital.”

Many questions remain about the effect of the virus. “We still have no idea why it makes children so ill”, says Bont. “We also do not know exactly how the illness develops or how to treat it effectively. There is currently no vaccine available. This is why I would like to explore the disease in more detail. So I went in search of a good model to set to work on it in the Netherlands.” 

Miniature organs
Bont came into contact with Norman Sachs, a cell biologist working in Hans Clevers’ group at the Hubrecht Institute. Sachs works on what are known as organoids, tiny organs made from adult stem cells, which earned Utrecht-based molecular geneticist Clevers worldwide acclaim. Sachs used this technique to develop miniature lungs. “These lung organoids are made up entirely of epithelial lung cells”, he explains, “including mucus producing cells and cells with cilia. These organoids are ideal for testing the effect of the virus and possible drugs.” To make organoids, we obtain lung tissue from cancer patients from whom human tissue samples have been taken as part of their treatment.

The two scientists have been allocated a Seed Money Grant to enable them to begin the work. “We have already succeeded in infecting the organoids”, says Sachs. “We will now investigate the differences between organoids of children who are ill and children who are not so affected. We also intend to compare the organoids of a child with those of an adult. This will enable us to see whether the lungs respond differently.” 

Government vaccination programme
Ultimately, the scientists hope to use the organoids model to develop a vaccine that can prevent the disease. “I expect that we will be able to develop a vaccine in 10 to 15 years. It will then be included in the government vaccination programme, to bring an end to HRSV in children”, says Bont. He does not expect it to result in fewer cases of the common cold. “Colds are caused by lots of other viruses as well.” 

This research is a perfect example of the excellent collaboration between the children’s hospital and the Hubrecht Institute. “We actually work together all the time”, explains Bont. “There have been joint projects focusing on intestine organoids, liver stem cells and cystic fibrosis.” Sachs adds: “Our location here in Utrecht could hardly be better. There is so much here: a university, an academic hospital, a children’s hospital, 3D printing facilities and, of course, the Hubrecht Institute. We could not do what we are doing anywhere else.”

Second Seed Money round
This is the second in a series of articles about the four research projects approved in the second Seed Money round for Life Sciences. It aims to bring together researchers from different disciplines to make joint proposals for pioneering research. The money can be used to collect research data that will serve as the basis for a grant application. Last year, six proposals were approved.

The four research partnerships approved in the second round are:

• Antimicrobial drugs optimisation by decoration with non-natural sugar variants Marc Wösten (Veterinary Medicine) / Roland Pieters (Science)

• Modefied Autologous prostasomes as a vaccine for prostate cancer Willem Stoorvogel (Veterinary Medicine) / Marianne Boes (UMC Utrecht)

• Human lung organoids: a novel model to understand respiratory syncytial virus bronchiolitis Louis Bont (UMC Utrecht) / Norman Sachs (Hubrecht Institute)

• Metabolic requirements for genome integrity in adult stem cells Boudewijn Burgering (UMC Utrecht) / Ruben van Boxtel (Hubrecht Institute)