Ex-Vivo Uterine Environment (EVE) Therapy Induced Limited Fetal Inflammation in a Premature Lamb Model.
Ex-Vivo Uterine Environment (EVE) Therapy Induced Limited Fetal Inflammation in a Premature Lamb Model.
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DOI：
10.1371/journal.pone.0140701
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kemp MW
中科院分区：
文献类型：
--
作者：
Miura Y;Saito M;Usuda H;Woodward E;Rittenschober-Böhm J;Kannan PS;Musk GC;Matsuda T;Newnham JP;Kemp MW
离体子宫环境（EVE）疗法使用人工胎盘为沉浸在羊水浴中的胎儿提供气体交换和营养输送。EVE的发展可能使我们能够在没有机械通气的情况下治疗极早产儿。同时，胎儿炎症的升高与不良的新生儿结局有关。在本研究中，我们分析了使用低预充量的平行脐带回路系统维持EVE治疗的早产羔羊的胎儿存活率、炎症和肺成熟。母羊在妊娠115天（足月150天）时接受手术分娩，胎儿被转移到EVE治疗组（EVE组; n = 5）。连续监测生理参数;间歇性采集胎儿血样以评估健康状况，并以参考范围值为目标，持续2天。在妊娠117天时，通过手术分娩与之匹配的动物（对照组; n = 6）。对两组的胎儿血液和组织样本进行分析和比较。EVE组的胎儿存活时间为27.0 ± 15.5（组平均值± SD）小时。只有一只胎仔完成了预定的研究期，具有最佳的生理参数，而其他4只动物在预定的研究终点之前表现出生理恶化或死亡。与对照组相比，在EVE组中观察到以下方面的显著升高（p<0.05）：i）胎儿血浆中的炎性蛋白; ii）胎儿组织中的选定细胞因子/趋化因子mRNA表达水平;和iii）胎儿肺中的组织学炎症评分。两组间表面活性蛋白mRNA表达水平无显著性差异（p>0.05）。在这项研究中，我们使用EVE治疗实现了有限的胎儿存活。尽管如此，EVE治疗仅诱导了适度的胎儿炎症反应，并没有促进肺成熟。这些数据为未来研究的评估提供了对治疗疗效标志物的额外见解。
Ex-vivo uterine environment (EVE) therapy uses an artificial placenta to provide gas exchange and nutrient delivery to a fetus submerged in an amniotic fluid bath. Development of EVE may allow us to treat very premature neonates without mechanical ventilation. Meanwhile, elevations in fetal inflammation are associated with adverse neonatal outcomes. In the present study, we analysed fetal survival, inflammation and pulmonary maturation in preterm lambs maintained on EVE therapy using a parallelised umbilical circuit system with a low priming volume. Ewes underwent surgical delivery at 115 days of gestation (term is 150 days), and fetuses were transferred to EVE therapy (EVE group; n = 5). Physiological parameters were continuously monitored; fetal blood samples were intermittently obtained to assess wellbeing and targeted to reference range values for 2 days. Age-matched animals (Control group; n = 6) were surgically delivered at 117 days of gestation. Fetal blood and tissue samples were analysed and compared between the two groups. Fetal survival time in the EVE group was 27.0 ± 15.5 (group mean ± SD) hours. Only one fetus completed the pre-determined study period with optimal physiological parameters, while the other 4 animals demonstrated physiological deterioration or death prior to the pre-determined study end point. Significant elevations (p<0.05) in: i) inflammatory proteins in fetal plasma; ii) selected cytokine/chemokine mRNA expression levels in fetal tissues; and iii) histological inflammatory score in fetal lung, were observed in the EVE group compared to the Control group. There was no significant difference (p>0.05) in surfactant protein mRNA expression level between the two groups. In this study, we achieved limited fetal survival using EVE therapy. Despite this, EVE therapy only induced a modest fetal inflammatory response and did not promote lung maturation. These data provide additional insight into markers of treatment efficacy for the assessment of future studies.