Rafat Neysan, Patry Christian, Sabet Ursula, Viergutz Tim, Weiss Christel, Tönshoff Burkhard, Beck Grietje, Schaible Thomas
Department of Neonatology, University Children's Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany.
Front Pediatr. 2019 Nov 22;7:490. doi: 10.3389/fped.2019.00490. eCollection 2019.
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. Peripheral blood mononuclear cells from newborns with ECMO-dependent ( = 18) and ECMO-independent CDH ( = 12) and from healthy controls ( = 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. 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%). 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.
内皮祖细胞(EPC)和间充质基质细胞(MSC)可使受损内皮再生,从而改善肺内皮功能障碍。我们尚不清楚体外膜肺氧合(ECMO)对先天性膈疝(CDH)患者中EPC和MSC介导的再生途径有何影响。因此,我们研究了ECMO支持是否会影响CDH患者的EPC和MSC数量。分离了依赖ECMO(n = 18)和不依赖ECMO的CDH新生儿(n = 12)以及健康对照者(n = 12)的外周血单个核细胞。通过流式细胞术鉴定EPC和MSC的数量。测定血管内皮生长因子(VEGF)和血管生成素(Ang)-2的血清水平。CDH新生儿的EPC和MSC数量升高。与不依赖ECMO的婴儿相比,依赖ECMO的婴儿在治疗前的EPC亚群计数更高(2.1 - 7.6倍)。在疾病过程中,依赖ECMO的婴儿的EPC和MSC亚群计数低于开始ECMO之前。在ECMO期间,VEGF血清水平显著降低(降低了90.5%)而Ang2水平显著升高(升高了74.8%)。我们的数据表明,ECMO可能与CDH新生儿中EPC和MSC的动员受损以及VEGF血清水平降低有关。