PCD is a rare inherited disorder in which the cilia in the airways do not function properly. As a result, mucus is cleared less effectively from the lungs.
Researchers at UMC Utrecht have developed a more affordable way to study Primary Ciliary Dyskinesia (PCD), a rare genetic lung disease. The new method makes it easier to compare multiple drugs and doses at the same time using cells from individual patients. This may help researchers better understand which treatments work best for which patient groups.
Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder in which the cilia in the airways do not function properly. As a result, mucus is not cleared effectively and accumulates in the lungs. This can lead to symptoms such as shortness of breath and recurrent lung infections.
“The causes of this disease vary from patient to patient,” says Gimano Amatngalim, assistant professor at the Regenerative Medicine Center Utrecht. “Cilia may be absent, move abnormally, or not move at all. That is why we aimed to develop a model that allows us to study the disease at the individual patient level.”
Researchers commonly use specialized culture systems in which stem cells grow on membranes exposed to nutrients below and air above. This air exposure is essential for the cells to develop into ciliated airway cells.
However, these systems are complex and expensive. “A standard culture plate costs around two euros, while these specialized plates can cost up to 250 euros each,” Amatngalim explains. “This makes it difficult to test multiple drugs and dosages for each individual patient.” To address this challenge, the researchers developed a more affordable alternative using standard culture plates.
The new method makes patient-specific research more accessible. Because it is more cost-effective and easier to scale, researchers can test multiple drugs and dosages simultaneously and better compare differences between patients.
This was previously difficult, as existing affordable models are not patient-specific. “As a result, they are less suitable for studying diseases that vary between individuals,” Amatngalim explains. “The new approach offers a middle ground: it resembles real airway cells while also enabling larger-scale studies.”
The new method does not fully replace existing models, which still more closely mimic the complexity of real airway tissue.“We therefore see this as a complementary approach,” Amatngalim says. “Researchers can first perform large-scale screening using the more affordable model, and then test the most promising treatments in the more advanced systems.”
The team now aims to further develop the method and apply it to other lung diseases, such as cystic fibrosis and asthma. This could make the approach more broadly applicable.
In the long term, this research may contribute to improved patient care. “We will be able to better understand what works, and for whom,” Amatngalim adds. “This allows us to tailor treatments more precisely and increase their effectiveness.”
In this new model, researchers investigated whether stem cells could develop into ciliated cells on standard culture plates. These plates contain nutrients on both sides and are not exposed to air. Initially, the stem cells showed limited development under these conditions.
The researchers found that air exposure itself is not the key factor. Instead, cellular processes triggered by low oxygen levels play a crucial role. By inhibiting these processes, they were able to successfully generate ciliated cells on standard plates. Importantly, these cells behaved similarly to those grown in conventional systems, including in drug testing experiments.
This research was conducted within the Lab of Cellular Disease Models, led by Jeffrey Beekman. The development and application of the model were carried out by PhD candidates Hetty Dreyer and Nefeli Ithakisiou, together with postdoctoral researcher Sacha Spelier. The project also included collaboration with Louis Bont, who at the time led Pediatric Infectious Diseases at the Wilhelmina Children’s Hospital (WKZ).
PCD is a rare inherited disorder in which the cilia in the airways do not function properly. As a result, mucus is cleared less effectively from the lungs.
Because the disease can differ from one patient to another. Cilia may be absent, move abnormally or be immotile, which means one model does not always reflect every patient well.
It uses standard culture plates, which are much cheaper than specialized systems. That makes it easier to test multiple drugs and doses at the same time and compareresults between patients.
No. The researchers describe it as a complementary model. It is especially useful for larger screening studies, while more advanced models are still needed for detailed follow-up work.
The team is also exploring whether the method can be used for other lung diseases, such as cystic fibrosis and asthma.