Data_Sheet_1_Endothelial Progenitor and Mesenchymal Stromal Cells in Newborns With Congenital Diaphragmatic Hernia Undergoing Extracorporeal Membrane Oxygenation.docx

Background: Endothelial progenitor (EPC) and mesenchymal stromal cells (MSC) can regenerate damaged endothelium and thereby improve pulmonary endothelial dysfunction. We do not know, how extracorporeal membrane oxygenation (ECMO) might affect EPC- and MSC-mediated regenerative pathways in patients with congenital diaphragmatic hernia (CDH). Therefore, we investigated, if ECMO support impacts EPC and MSC numbers in CDH patients.Methods: Peripheral blood mononuclear cells from newborns with ECMO-dependent (n = 18) and ECMO-independent CDH (n = 12) and from healthy controls (n = 12) were isolated. The numbers of EPC and MSC were identified by flowcytometry. Serum levels of vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-2 were determined.Results: EPC and MSC were elevated in newborns with CDH. ECMO-dependent infants had higher EPC subpopulation counts (2,1–7,6-fold) before treatment compared to ECMO-independent infants. In the disease course, EPC and MSC subpopulation counts in ECMO-dependent infants were lower than before ECMO initiation. During ECMO, VEGF serum levels were significantly reduced (by 90.5%) and Ang2 levels significantly increased (by 74.8%).Conclusions: Our data suggest that ECMO might be associated with a rather impaired mobilization of EPC and MSC and with a depression of VEGF serum levels in newborns with CDH.

背景：内皮祖细胞（EPC）和间充质干细胞（MSC）能够再生受损的内皮，从而改善肺内皮功能障碍。关于体外膜肺氧合（ECMO）可能如何影响患有先天性膈疝（CDH）的患者的EPC和MSC介导的再生途径，我们尚不清楚。因此，我们研究了ECMO支持是否会影响CDH患者的EPC和MSC数量。方法：从依赖ECMO的婴儿（n = 18）、非ECMO依赖性CDH（n = 12）和健康对照组（n = 12）的新生儿中分离出外周血单个核细胞。通过流式细胞术确定EPC和MSC的数量。检测血清中血管内皮生长因子（VEGF）和血管生成素（Ang）-2的水平。结果：在患有CDH的新生儿中，EPC和MSC的数量升高。与依赖ECMO的婴儿相比，非ECMO依赖性婴儿在接受治疗前的EPC亚群计数（2.1-7.6倍）较高。在疾病过程中，依赖ECMO的婴儿的EPC和MSC亚群计数低于ECMO开始之前。在ECMO期间，VEGF血清水平显著降低（降低90.5%），Ang2水平显著增加（增加74.8%）。结论：我们的数据表明，ECMO可能与EPC和MSC的动员受损以及新生儿的CDH中VEGF血清水平的降低有关。