Published ahead of print on July 2, 2009, doi:10.1164/rccm.200812-1949OC Am. J. Respir. Crit. Care Med., Volume 180, Number 6, September 2009, 540-546 A more recent version of this article appeared on September 15, 2009
Submitted on December 26, 2008 Circulating Endothelial Progenitor Cells in Preterm Infants with Bronchopulmonary DysplasiaAlessandro Borghesi1*,1 Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, 2 Biotechnology Laboratory, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, 3 Clinical Epidemiology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, 4 Department of Biometry and Statistics, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, 5 Department of Obstetrics and Gynecology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, 6 Organ Transplantation Laboratory, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy * To whom correspondence should be addressed. E-mail: alessandroborghesi{at}yahoo.it.
Rationale: The new form of bronchopulmonary dysplasia (BPD) is characterized by lung immaturity with disrupted alveolar and capillary development after extremely premature birth, but the mechanism of impaired lung vascular formation is still not completely understood. Objectives: We tested the hypothesis that reduced numbers of circulating endothelial progenitor cells at birth are associated with the development of BPD. Methods: We studied ninety-eight preterm infants with gestational age < 32 weeks or birth weight < 1500 g. Endothelial colony forming cells (ECFCs) were assessed by clonogenic analysis in infants for whom cord blood was available. The proportion of circulating endothelial and hematopoietic cells was measured at birth, at 48 hours and at 7 days of life by flow cytometry. Measurements and Main Results: ECFCs in cord blood were lower in infants who later developed BPD (median [range]: 0.00 [0.00-0.48] vs 2.00 [0.00-21.87], P = 0.002). ECFCs decreased with decreasing gestational age (r = 0.41, P = 0.02), but even at extremely low gestational ages infants with higher numbers of ECFCs were protected from BPD. The endothelial and hematopoietic cell subsets studied by flow cytometry were comparable in infants with and without BPD, and rapidly decreased after birth. Conclusions: ECFCs are low at extremely low gestational ages and increase during gestation; extremely preterm infants who display lower numbers at birth have an increased risk of developing BPD. Our findings suggest that decreased ECFCs following extremely preterm birth may be associated with the risk for developing lung vascular immaturity characteristic of new BPD. Key words: newborn • EPC • HPC • Endothelial colony forming cell • chronic lung disease of prematurity
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