Dangerous malformation of the newborn lungs is associated with inflammatory processes involving the increased presence of immune cells.
RT’s Three Key Takeaways:
- Research has identified that inflammation in the epithelial cells of the fetal lungs, particularly in cases of congenital diaphragmatic hernia, is a factor in preventing full lung development before birth. This inflammation is associated with the presence of macrophages, which are immune cells that may trigger this inflammatory response.
- Previous studies have demonstrated that the steroid dexamethasone, commonly administered to pregnant women at risk of preterm delivery, can improve lung maturation in fetuses affected by congenital diaphragmatic hernia. This finding opens the door for potential therapeutic applications to mitigate the effects of this condition.
- Collaborative research has shown that extracellular vesicles derived from amniotic fluid stem cells can reduce inflammation and promote lung development in animal models of congenital diaphragmatic hernia. However, further research is needed to understand the broader implications of this approach before it can be considered for human therapy.
Congenital diaphragmatic hernia, affecting about 1 in 2,500 babies, causes a hole in the fetus’ diaphragm and, through unexplained processes, prevents the lungs from developing fully before birth. Nearly a third of affected babies die as a result.
“We have known that congenital lung underdevelopment in diaphragmatic hernia is associated with inflammatory processes at the molecular level since we compared the molecular properties of stem cells from normal and underdeveloped lungs of patients with this condition,” says Dr Richard Wagner, assistant physician and research group leader for pediatric surgery at the University of Leipzig Medical Center, in a release. “In that study, we were able to show that lung maturation can be significantly improved by drug therapy with dexamethasone.”
In everyday clinical practice, this steroid is already given to pregnant women who are at risk of preterm delivery. It helps the fetus’ lungs to develop as well as possible at an early stage.
Immune Cells in Underdeveloped Lungs
“In a subsequent study, we were able to show that it is primarily the epithelial cells of the lung that are affected by inflammation,” says the scientist in a release. “They are the cells that are located on the surface layer of the lungs and come into contact with the amniotic fluid.”
Inflammation could explain why lung development stagnates. “If an organ has to deal with an inflammatory reaction during development, this will impair organ differentiation and growth,” says Wagner in a release.
In animal models and in the lungs of human patients, the researchers found specific pro-inflammatory signaling processes there that correlate with an accumulation of macrophages, which are immune system scavenger cells. It is not yet known why these are more likely to migrate to the fetal lungs and possibly trigger the inflammation.
Anti-inflammatory Effect of Cellular Components from Amniotic Fluid
Scientists in Toronto, with whom the Leipzig researchers are collaborating, took a slightly different therapeutic approach. In a recently published study, they also found inflammatory processes and increased immune cells in animal models of congenital diaphragmatic hernia.
So-called extracellular vesicles from stem cells, which the researchers had isolated from the amniotic fluid and multiplied, proved effective against the inflammatory changes. These vesicles are cellular components that move from cell to cell, carrying complex information—including genetic blueprints, such as RNA particles.
In animal models, the researchers found that when they administered such vesicles to pregnant animals, the inflammation was reduced and the lungs of the fetuses were able to develop more normally. However, this method is still a long way from being a potential therapy for humans: “For example, we still need to investigate in detail how the vesicles affect other organ systems in the fetus,” says Wagner in a release.
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