Phospholipid Profile of Amniotic Fluid in Ovine Model of Congenital Diaphragmatic Hernia (CDH): The Effect of Fetal Tracheal Occlusion

2015 ◽  
Vol 14 (3) ◽  
pp. 1465-1471 ◽  
Author(s):  
Maria Chiara Mimmi ◽  
Maurizio Ballico ◽  
Francesco Amoroso ◽  
Valeria Calcaterra ◽  
Mario Marotta ◽  
...  

2017 ◽  
Vol 37 (10) ◽  
pp. 1046-1049 ◽  
Author(s):  
Viola Seravalli ◽  
Eric B. Jelin ◽  
Jena L. Miller ◽  
Aylin Tekes ◽  
Luca Vricella ◽  
...  




2022 ◽  
Author(s):  
Kasra Khalaj ◽  
Rebeca Lopes Figueira ◽  
Lina Antounians ◽  
Sree Gandhi ◽  
Matthew Wales ◽  
...  

Pulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH) is characterized by impaired branching morphogenesis and differentiation. We have previously demonstrated that administration of extracellular vesicles derived from rat amniotic fluid stem cells (AFSC-EVs) rescues development of hypoplastic lungs at the pseudoglandular and alveolar stages in rodent models of CDH. Herein, we tested whether AFSC-EVs exert their regenerative effects at the canalicular and saccular stages, as these are translationally relevant for clinical intervention. To induce fetal pulmonary hypoplasia, we gavaged rat dams with nitrofen at embryonic day 9.5 and demonstrated that nitrofen-exposed lungs had impaired branching morphogenesis, dysregulated signaling pathways relevant to lung development (FGF10/FGFR2, ROBO/SLIT, Ephrin, Neuropilin 1, beta-catenin) and impaired epithelial and mesenchymal cell marker expression at both stages. AFSC-EVs administered to nitrofen-exposed lung explants rescued airspace density and increased the expression levels of key factors responsible for branching morphogenesis. Moreover, AFSC-EVs rescued the expression of alveolar type 1 and 2 cell markers at both canalicular and saccular stages, and restored markers of club, ciliated epithelial, and pulmonary neuroendocrine cells at the saccular stage. AFSC-EV treated lungs also had restored markers of lipofibroblasts and PDGFRA+ cells to control levels at both stages. EV tracking showed uptake of AFSC-EV RNA cargo throughout the fetal lung and an mRNA-miRNA network analysis identified that several miRNAs responsible for regulating lung development processes were contained in the AFSC-EV cargo. These findings suggest that AFSC-EV based therapies hold potential for restoring fetal lung growth and maturation in babies with pulmonary hypoplasia secondary to CDH.



Author(s):  
Felipe Fromm ◽  
Katharina Wenke ◽  
Thomas Krebs ◽  
Michael Boettcher ◽  
Georg Eschenburg ◽  
...  

Background Severe congenital diaphragmatic hernia (CDH) is prenatally managed by fetoscopic tracheal occlusion (FETO) to improve lung growth and maturation. As FETO is not able to reduce the pressure onto the developing lungs originating from the intestine growing into the thoracic cavity, fetal abdominal decompression may alleviate this pressure effect by directing the growing intestine into the amniotic cavity away from the lungs. Therefore, aim of this study was to establish an animal model for fetoscopic abdominal decompression in fetal sheep with CDH. Methods CDH was created surgically on day 75 of 145 day gestation in eight fetuses. 2-3 weeks later, an opening was created in the fetal abdomen by fetoscopic surgery. The fetuses were retrieved by cesarean section at the end of pregnancy and evaluated. Results Five fetuses with CDH were treated with fetoscopic abdominal decompression. Three fetuses with CDH were taken as controls. One fetus was lost after creation of the CDH and two other after creation of the abdominal defect. Preliminary sterological results showed that the septal thickness of the experimental group was smaller than in the CDH group. Conclusion This study demonstrates the general feasibility of fetoscopic abdominal decompression for diaphragmatic hernia in our new animal model. Although not statistically significant, the lungs of treated fetuses were larger and heavier than those of untreated controls. Our findings support the hypothesis of palliative fetal surgery for severe CDH compared to tracheal occlusion. More controlled animal trials are needed.





2020 ◽  
Vol 8 ◽  
Author(s):  
Francesco Macchini ◽  
Anna Morandi ◽  
Stefano Mazzoleni ◽  
Martina Ichino ◽  
Giacomo Cavallaro ◽  
...  


2020 ◽  
Vol 46 (12) ◽  
pp. 2598-2604
Author(s):  
Seiji Wada ◽  
Katsusuke Ozawa ◽  
Rika Sugibayashi ◽  
Fumio Suyama ◽  
Shoichiro Amari ◽  
...  


2019 ◽  
Vol 104 (6) ◽  
pp. F609-F616 ◽  
Author(s):  
Philip L J DeKoninck ◽  
Kelly J Crossley ◽  
Aidan J Kashyap ◽  
Sasha M Skinner ◽  
Marta Thio ◽  
...  

ObjectiveFetoscopic endoluminal tracheal occlusion (FETO) aims to reverse pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) and mitigate the associated respiratory insufficiency and pulmonary hypertension after birth. We aimed to determine whether FETO improves the cardiopulmonary transition at birth in an ovine model of CDH.MethodsIn 12 ovine fetuses with surgically induced diaphragmatic hernia (DH; 80 dGA), an endotracheal balloon was placed tracheoscopically at ≈110 dGA and removed at ≈131 dGA (DH+FETO), while 10 were left untreated (DH). At ≈138 dGA, all lambs (survival at delivery: 67% [DH+FETO], 70% [DH]) were delivered via caesarean section and ventilated for 2 hours. Physiological and ventilation parameters were continuously recorded, and arterial blood-gas values were measured.ResultsCompared with DH, DH+FETO lambs had increased wet lung-to-body-weight ratio (0.031±0.004 vs 0.016±0.002) and dynamic lung compliance (0.7±0.1 vs 0.4±0.1 mL/cmH2O). Pulmonary vascular resistance was lower in DH+FETO lambs (0.44±0.11 vs 1.06±0.17 mm Hg/[mL/min]). However, after correction for lung weight, pulmonary blood flow was not significantly different between the groups (4.19±0.57 vs 4.05±0.60 mL/min/g). Alveolar–arterial difference in oxygen tension was not significantly different between DH+FETO and DH (402±41mm Hg vs 401±45 mm Hg).ConclusionsFETO accelerated lung growth in fetuses with CDH and improved neonatal respiratory function during the cardiopulmonary transition at birth. However, despite improved lung compliance and reduced pulmonary vascular resistance, there were less pronounced benefits for gas exchange during the first 2 hours of life.



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