Endothelial Colony-forming Cells from Preterm Infants Are Increased and More Susceptible to Hyperoxia

Abstract

Rationale: Preterm birth and hyperoxic exposure increase the risk for bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by impaired vascular and alveolar growth. Endothelial progenitor cells, such as self-renewing highly proliferative endothelial colony-forming cells (ECFCs), may participate in vascular repair. The effect of hyperoxia on ECFC growth is unknown. Objectives: We hypothesize that umbilical cord blood (CB) from premature infants contains more ECFCs with greater growth potential than term CB. However, preterm ECFCs may be more susceptible to hyperoxia. Methods: ECFC colonies were quantified by established methods and characterized by immunohistochemistry and flow cytometry. Growth kinetics were assessed in room air and hyperoxia (FI O 2 5 0.4). Measurements and Main Results: Preterm CB (28-35 wk gestation) yielded significantly more ECFC colonies than term CB. Importantly, we found that CD45 2 /CD34 1 /CD133 1 /VEGFR-2 1 cell number did not correlate with ECFC colony count. Preterm ECFCs demonstrated increased growth compared with term ECFCs. Hyperoxia impaired growth of preterm but not term ECFCs. Treatment with superoxide dismutase and catalase enhanced preterm ECFC growth during hyperoxia. Conclusions: Preterm ECFCs appear in increased numbers and proliferate more rapidly but have an increased susceptibility to hyperoxia compared with term ECFCs. Antioxidants protect preterm ECFCs from hyperoxia.

Intravenous Administration of Endothelial Colony-Forming Cells Overexpressing Integrin β1 Augments Angiogenesis in Ischemic Legs

“…EPCs consist of diverse progenitor-like cell populations, including early-outgrowth EPCs and late-outgrowth endothelial colonyforming cells (ECFCs). Unlike early EPCs, ECFCs have an endothelial morphology, express endothelial markers, are highly proliferative, and exhibit a progenitor-like capacity for self-renewal [7][8][9][10].…”

MicroRNA Expression Profile in Hyperoxia-Exposed Newborn Mice During the Development of Bronchopulmonary Dysplasia

“…1,2 Although the incidence and severity of respiratory distress syndrome have decreased with antenatal corticosteroid therapy and postnatal surfactant replacement, the overall incidence of BPD has been increasing. 3,4 BPD is predominantly characterized by persistent abnormalities of lung structure and arrested lung development, including impaired alveolar and vascular growth.…”

“…3,4 BPD is predominantly characterized by persistent abnormalities of lung structure and arrested lung development, including impaired alveolar and vascular growth. 1,5 The pathogenesis of BPD is not fully understood.…”

Endothelial Colony‐Forming Cells in Young Adults Born Preterm: A Novel Link Between Neonatal Complications and Adult Risks for Cardiovascular Disease

“…In the cord blood of preterm infants, EPC counts have been shown to be either similar to or increased versus full‐term infants, but studies of ECFC subtype proliferation and vessel formation have yielded contradictory results 54. Cord blood ECFC from preterm infants were shown to be particularly vulnerable to oxidant conditions (such as hyperoxia) with drastically impaired growth potential, disrupted nitric oxide/vascular endothelial growth factor signaling, accelerated cell senescence, as well as increased oxidative stress status 16, 17, 55. In addition, human fetal lung ECFC and newborn rat ECFC function are also impaired after high oxygen exposure (mimicking preterm birth conditions) 36.…”

“…However, preterm birth is associated with perinatal conditions that are deleterious for organ development, and often inherently prooxidative (including the major rise in po 2 occurring during the transition from fetal to extrauterine life) and proinflammatory in nature 14, 15. Importantly, studies have shown that EPC of preterm infants, more specifically the subpopulation of endothelial colony‐forming cells (ECFC), have an increased vulnerability to hyperoxia‐induced oxidative stress resulting in cell dysfunction 16, 17. ECFC, although highly present in the cord blood of newborn infants, are only found in very low quantities in the peripheral circulation of adults 12, 18, 19.…”