Congenital diaphragmatic hernia (CDH) is a serious condition affecting the lungs and diaphragm, leading to nearly one-third of impacted infants experiencing fatal respiratory issues due to underdeveloped lungs. Researchers have made significant strides in understanding this condition. They have identified a link between the harmful lung malformation in newborns and inflammatory responses that increase the number of immune cells present. Additionally, another study indicates that elements derived from amniotic fluid stem cells may offer anti-inflammatory benefits.
Congenital diaphragmatic hernia (CDH) is a serious condition affecting the lungs and diaphragm, leading to nearly one-third of impacted infants experiencing fatal respiratory issues due to underdeveloped lungs. Researchers have made significant strides in understanding this condition. They have identified a link between the harmful lung malformation in newborns and inflammatory responses that increase the number of immune cells present. Additionally, another study indicates that elements derived from amniotic fluid stem cells may offer anti-inflammatory benefits.
CDH occurs in approximately 1 in every 2500 births and creates a defect in the fetus’ diaphragm. This defect leads to impairments in lung development before birth, contributing to high mortality rates among affected infants. “We have recognized that the lack of lung development in diaphragmatic hernia cases correlates with inflammation at the molecular level, particularly when comparing stem cell properties between normal and underdeveloped lungs,” remarks PD Dr Richard Wagner, an assistant physician and leader of a pediatric surgery research group at the University of Leipzig Medical Center. “Our research established that administering dexamethasone can significantly improve lung maturation,” he adds. In clinical practice, this steroid is commonly provided to pregnant women at risk of premature labor to help optimize fetal lung development at an early stage.
Inflammatory Responses in Immature Lungs
“In further studies, we discovered that inflammation primarily affects the epithelial cells of the lungs,” states Wagner. “These surface-level cells come into direct contact with amniotic fluid.” The presence of inflammation may hinder lung development. “If an organ faces an inflammatory response during its formation, this can disrupt its growth and cellular differentiation,” he explains. In both animal models and among patients, researchers identified specific pro-inflammatory signaling pathways linked to an increase in macrophages—immune cells that clear away debris. The exact reasons behind the migration of these cells to fetal lungs and their potential role in inducing inflammation remain unclear.
Potential Anti-inflammatory Properties of Amniotic Fluid Components
Scientists in Toronto, collaborating with the Leipzig research team, explored a different therapeutic angle. In a recently published study, they observed similar inflammatory responses and elevated immune cell levels in animal models of CDH.
They isolated and expanded extracellular vesicles from amniotic fluid stem cells, which demonstrated effectiveness against inflammatory changes. These vesicles are cell-derived elements that facilitate communication between cells by transferring complex information, including genetic instructions like RNA particles. In animal models, administering these vesicles to pregnant subjects led to reduced inflammation and healthier fetal lung development. However, translating this approach into human therapy still requires extensive investigation: “We need to thoroughly explore how these vesicles influence other fetal organ systems,” notes Wagner.
The collaboration with research teams in Boston, US, and Winnipeg and Toronto, Canada, began during Dr. Richard Wagner’s year and a half as a postdoctoral researcher in North America, focusing on lung underdevelopment linked to diaphragmatic hernia. His research in this domain has earned him several accolades, including the Richard Drachter Award from the German Society of Pediatric and Adolescent Surgery in April.