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. 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. 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. 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. N/A (animal and laboratory study).

中文翻译：

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产前给予羊水干细胞来源的细胞外囊泡可改善患有先天性膈疝的新生大鼠的肺功能

肺发育不全的严重程度是先天性膈疝（CDH）婴儿预后的主要决定因素。产前给予羊水干细胞衍生的细胞外囊泡 (AFSC-EV) 已被证明可以挽救 CDH 大鼠除草醚模型中肺发育的形态特征。在此，我们评估了对患有 CDH 的胎鼠施用 AFSC-EV 是否与新生儿肺功能的改善相关。通过超速离心分离 AFSC-EV，并通过大小、形态和典型标记表达进行表征。在胚胎 (E) 第 9.5 天，母鼠用橄榄油（对照）或除草醚强饲以诱导 CDH。在 E18.5，胎儿接受了羊膜内注射生理盐水或 AFSC-EV。在 E21.5，大鼠被分娩并进行气管切开术以进行机械通气（flexiVent 系统）。比较各组的肺顺应性、阻力、牛顿阻力、组织阻尼和弹性。评估肺的分支形态发生和胶原定量。与健康对照相比，经盐水处理的 CDH 幼犬的气腔较少，胶原蛋白沉积较多，并且功能上表现出顺应性降低，气道阻力、弹性和组织阻尼增加。相反，AFSC-EV 给药导致肺力学（顺应性、阻力、组织阻尼、弹性）以及肺分支形态发生和胶原沉积的改善。我们的研究表明，大鼠除草醚模型重现了与患有 CDH 的人类婴儿相似的肺功能损伤。产前给予 AFSC-EV 可改善患有 CDH 的新生大鼠的肺形态和功能。 N/A（动物和实验室研究）。