AI Article Synopsis
- This study investigates the effects of amniotic fluid stem cell-derived extracellular vesicles (AFSC-EVs) on lung development in fetal rats with congenital diaphragmatic hernia (CDH), a condition affecting respiratory function in newborns.
- Researchers induced CDH in pregnant rats and then administered AFSC-EVs to the fetuses before birth, comparing their lung function and morphology to control pups that didn't receive the treatment.
- Results showed that pups treated with AFSC-EVs had improved lung mechanics, structure, and reduced collagen deposition compared to those treated with saline, suggesting potential therapeutic benefits for managing CDH-related lung impairment in neonates.
Article Abstract
Background: The severity of pulmonary hypoplasia is a main determinant of outcome for babies with congenital diaphragmatic hernia (CDH). Antenatal administration of extracellular vesicles derived from amniotic fluid stem cells (AFSC-EVs) has been shown to rescue morphological features of lung development in the rat nitrofen model of CDH. Herein, we evaluated whether AFSC-EV administration to fetal rats with CDH is associated with neonatal improvement in lung function.
Methods: AFSC-EVs were isolated by ultracentrifugation and characterized by size, morphology, and canonical marker expression. At embryonic (E) day 9.5, dams were gavaged with olive oil (control) or nitrofen to induce CDH. At E18.5, fetuses received an intra-amniotic injection of either saline or AFSC-EVs. At E21.5, rats were delivered and subjected to a tracheostomy for mechanical ventilation (flexiVent system). Groups were compared for lung compliance, resistance, Newtonian resistance, tissue damping and elastance. Lungs were evaluated for branching morphogenesis and collagen quantification.
Results: Compared to healthy control, saline-treated pups with CDH had fewer airspaces, more collagen deposition, and functionally exhibited reduced compliance and increased airway resistance, elastance, and tissue damping. Conversely, AFSC-EV administration resulted in improvement of lung mechanics (compliance, resistance, tissue damping, elastance) as well as lung branching morphogenesis and collagen deposition.
Conclusions: Our studies show that the rat nitrofen model reproduces lung function impairment similar to that of human babies with CDH. Antenatal administration of AFSC-EVs improves lung morphology and function in neonatal rats with CDH.
Level Of Evidence: N/A (animal and laboratory study).
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| http://dx.doi.org/10.1016/j.jpedsurg.2024.02.029 | DOI Listing |
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