With stem cell model on the trail of congenital diaphragmatic hernia

Researchers have designed a new stem cell model to study congenital diaphragmatic hernia in newborns with underdeveloped lungs. They were able to isolate stem cells from the fluid that is suctioned from the baby’s lungs and normally gets discarded and use them as a foundation for the model.

In this MEDICA-tradefair.com interview, Dr. Richard Wagner explains how the stem cell model works and reveals the insights the researchers have gained from this method.

Dr. Wagner, what inspired the idea for the new stem cell model?

Dr. Richard Wagner: Our research pertaining to congenital diaphragmatic hernia in newborns revealed that there are still no models that facilitate the testing of therapeutic approaches on living human lung tissue. Congenital diaphragmatic hernia is a defect in the diaphragm of an unborn baby combined with a form of underdeveloped lungs, which even today causes many affected newborns to die. We want to improve the situation and have been in search of a human cell model that allows us to test various aspects of congenital diaphragmatic hernia. Since the lungs are underdeveloped, they are too small, making it impossible to remove some additional tissue during congenital diaphragmatic hernia repair for further exams. Meanwhile, airway suctioning is already an established method and there has been research into the isolation of stem cells from the lungs. However, the isolation of stem cells in newborns with congenital diaphragmatic hernia is a new approach.

How does the stem cell model work?

Wagner: Since the lungs are not fully developed, the newborns are intubated and placed on a ventilator immediately after birth. Because they cannot cough on their own as they are under assisted ventilation, their airways are suctioned on a regular basis. We take the lung tissue acquired from the airway suctioning and use it as a surrogate tissue for our model. The harvested stem cells allow us to differentiate them into different lung tissues, which we can subsequently cultivate and develop in the laboratory. This allows us to model the bronchial epithelium, the uppermost layer of the bronchial cells in the airways. These are the cells that line the bronchi in the lungs. Ultimately, this provides us with a patient-specific sample in which we can identify the genes that are active in the cells. This permits us to discern pathological cellular adaptations. We can also test for epigenetic changes in the stem cell model. This allows the detection of molecular differences between the stem cells in newborns with congenital diaphragmatic hernia and control patients. We were able to identify an abnormal differentiation pattern.

What were the biggest challenges you faced in researching the new stem cell model?

Wagner: The last 1.5 years we focused on intensive research into the stem cell model. Needless to say, we encountered several obstacles as things can sometimes go wrong with cell models. For example, the cells can become infected, which means they won’t grow normally and must be discarded. You lose a sample, if this happens to the cells of affected newborns that have not yet been multiplied in the laboratory. The research logistics of this are likewise complex. The process requires a lot of staff starting with intubation, suctioning, sample storage, cell isolation and cell proliferation in the laboratory.

What insights did you gain from the stem cell model study?

Wagner: We were able to create a new model that allows the first-ever analysis of changes in the cells of human newborns with a congenital diaphragmatic hernia. These changes also correlate with those already observed in acknowledged animal models. We can make a positive impact on the changes via a treatment that slows down the inflammatory reaction.

What new research opportunities could result from these insights?

Wagner: The cell model allows the testing of a wide variety of therapeutic agents. Prior to this, tests on living tissue from newborns with a diaphragmatic hernia were not possible. The cell model could also serve as a kind of bridge between the animal model and therapy attempts with humans. Immune cells, connective tissue cells (fibrocytes) and pneumocytes also have functions in the lungs. Future research could use the model to study them in more detail.