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More about congenital diaphragmatic hernia
same diagnosisDive deeper → Congenital Diaphragmatic Hernia (21 items)Video
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What the experts said
Congenital diaphragmatic hernia is characterized by impaired fetal lung growth and maturation with unacceptably high mortality and morbidity rates.
One of the biggest challenges for babies with CDH is that fetal hypoplastic lungs are immature with impairment of cell differentiation, especially in the epithelium.
Extracellular vesicles (EVs) are the main mediators of stem cell paracrine signaling.
Amniotic fluid stem cell derived EVs can rescue fetal lung growth and maturation in several models of CDH at the pseudoglandular stage, which corresponds to 7 to 16 weeks of human gestation.
CDH is diagnosed around 18 to 20 weeks gestation.
The nitrophin model is a well-established model for studying CDH, created by administering the herbicide nitrophin to pregnant rat dams at embryonic day 9.5.
Hypoplastic lungs at canalicular and saccular stages show down-regulation of alveolar type 1 and 2 cells, as well as basal and club cells compared to control.
Treatment of hypoplastic lungs with amniotic fluid stem cell derived extracellular vesicles restores primary markers of alveolar type 1 and 2 cells, basal cells, and club cells, indicating that cell homeostasis can be achieved.
Most babies with congenital diaphragmatic hernia are diagnosed halfway during pregnancy, creating a window for potential prenatal interventions before birth.
In vivo experiments have been performed in a rat model using different administration routes including intraamniotic and tracheal, with promising results.
There is active collaboration with Dr. Jan De Prest to investigate the safety and feasibility of EV treatment in a lab model.
Ciliated cells did not show a difference with EV treatment, potentially due to an imbalance of different cell types in the hypoplastic fetal lung creating a different homeostatic cell composition.
Key markers expressed in branching morphogenesis are being rescued effectively by EV treatment, suggesting the importance is the greater cell homeostatic balance rather than any specific cell type.