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

¹ Pediatric Heart Lung Center, University of Colorado Denver School of Medicine, Denver; ² The Children's Hospital, Aurora, Colorado; and ³ Indiana University School of Medicine, Indianapolis, Indiana

Correspondence and requests for reprints should be addressed to Christopher D. Baker, M.D., Pediatric Heart Lung Center, University of Colorado Denver, Mail Stop 8317, 12800 E. 19th Ave., Aurora, CO 80045. E-mail: christopher.baker{at}uchsc.edu

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_O2 = 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^–/CD34⁺/CD133⁺/VEGFR-2⁺ 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.

Key Words: endothelial progenitor cells • bronchopulmonary dysplasia • umbilical cord blood • reactive oxygen species • antioxidants

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Endothelial progenitor cells (EPCs) are mobilized in response to lung injury. Umbilical cord blood is a rich source of circulating EPCs, but the role of EPCs during prenatal vascular development is unknown. What This Study Adds to the Field A specific subgroup of EPCs, endothelial colony-forming cells (ECFCs) are increased in preterm cord blood. Compared to term ECFCs, preterm ECFCs proliferate more rapidly but are more sensitive to hyperoxia, a known contributor to bronchopulmonary dysplasia.

 

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