Abstract
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.
Highlights
Severe congenital diaphragmatic hernia (CDH) in newborns is accompanied by pronounced hypoplasia of both pulmonary tissue and the pulmonary vasculature [1]
Relative lung volume were inversely correlated with numbers of endothelial progenitor cells (EPC)-CD45dim/CD34+/CD133+
At day 0, vascular endothelial growth factor (VEGF) serum levels did not differ significantly in all three groups, yet in the disease course VEGF serum levels were significantly reduced in the EMCO-dependent group but remained stable in the Extracorporeal membrane oxygenation (ECMO)-independent and in the healthy control group (Figure 3, Supplemental Table S4)
Summary
Severe congenital diaphragmatic hernia (CDH) in newborns is accompanied by pronounced hypoplasia of both pulmonary tissue and the pulmonary vasculature [1]. To improve survival and outcome of severe forms of CDH, therapies are needed that resolve pulmonary hypertension and the underlying hypoplasia of pulmonary tissue, such as therapeutic measures to promote growth of the pulmonary vasculature. In this respect, endothelial progenitor cells (EPC) and mesenchymal stromal cells (MSC) appear to be interesting potential research targets, since they have been demonstrated to promote angiogenesis and endothelial cell regeneration in several diseases with underlying endothelial dysfunction and damage in numerous experimental and pre-clinical studies [6, 7]. We investigated, if ECMO support impacts EPC and MSC numbers in CDH patients
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