Endothelial progenitor cells, bronchopulmonary dysplasia and other short-term outcomes of extremely preterm birth

Paviotti, Giulia; Fadini, Gian Paolo; Boscaro, Elisa; Agostini, Carlo; Avogaro, Angelo; Chiandetti, Lino; Baraldi, Eugenio; Filippone, Marco

doi:10.1016/j.earlhumdev.2011.03.011

Cited by 27 publications

(47 citation statements)

References 39 publications

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“…However, we did not measure these cells as they are not different in the cord blood of full-term infants and preterm infants whether or not they later develop BPD [19, 31]. In contrast, CPCs express a different surface antigen profile (CD45-dim CD34+ CD31+ AC133+), are proangiogenic and promote tumour growth in vivo [22].…”

Section: Discussionmentioning

confidence: 99%

Cord blood angiogenic progenitor cells are decreased in bronchopulmonary dysplasia

et al. 2012

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Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is associated with impaired vascular and alveolar growth. Antenatal factors contribute to the risk for developing BPD by unclear mechanisms. Endothelial progenitor cells, such as angiogenic circulating progenitor cells (CPCs) and late-outgrowth endothelial colony-forming cells (ECFCs), may contribute to angiogenesis in the developing lung. We hypothesise that cord blood angiogenic CPCs and ECFCs are decreased in preterm infants with moderate and severe BPD. We quantified ECFCs and the CPC/nonangiogenic-CPC ratio (CPC/non-CPC) in cord blood samples from 62 preterm infants and assessed their relationships to maternal and perinatal risk factors as well as BPD severity. The CPC/non-CPC ratio and ECFC number were compared between preterm infants with mild or no BPD and those with moderate or severe BPD. ECFC number (p<0.001) and CPC/non-CPC ratio (p<0.05) were significantly decreased in cord blood samples of preterm infants who subsequently developed moderate or severe BPD. Gestational age and birth weight were not associated with either angiogenic marker. Circulating vascular progenitor cells are decreased in the cord blood of preterm infants who develop moderate and severe BPD. These findings suggest that prenatal factors contribute to late respiratory outcomes in preterm infants.

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Section: Discussionmentioning

confidence: 99%

Cord blood angiogenic progenitor cells are decreased in bronchopulmonary dysplasia

et al. 2012

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“…Bronchopulmonary dysplasia (BPD) was diagnosed based on requirement of oxygen supplementation at 36 weeks postmenstrual age (PMA) and abnormal findings on chest radiography [12-14]. …”

Section: Methodsmentioning

confidence: 99%

Circulating hematopoietic stem cell count is a valuable predictor of prematurity complications in preterm newborns

et al. 2012

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BackgroundThe frequency of preterm labour has risen over the last few years. Hence, there is growing interest in the identification of markers that may facilitate prediction and prevention of premature birth complications. Here, we studied the association of the number of circulating stem cell populations with the incidence of complications typical of prematurity.MethodsThe study groups consisted of 90 preterm (23–36 weeks of gestational age) and 52 full-term (37–41 weeks) infants. Non-hematopoietic stem cells (non-HSCs; CD45-lin-CD184+), enriched in very small embryonic-like stem cells (VSELs), expressing pluripotent (Oct-4, Nanog), early neural (β-III-tubulin), and oligodendrocyte lineage (Olig-1) genes as well as hematopoietic stem cells (HSCs; CD45+lin-CD184+), and circulating stem/progenitor cells (CSPCs; CD133+CD34+; CD133-CD34+) in association with characteristics of prematurity and preterm morbidity were analyzed in cord blood (CB) and peripheral blood (PB) until the sixth week after delivery. Phenotype analysis was performed using flow cytometry methods. Clonogenic assays suitable for detection of human hematopoietic progenitor cells were also applied. The quantitative parameters were compared between groups by the Mann–Whitney test and between time points by the Friedman test. Fisher’s exact test was used for qualitative variables.ResultsWe found that the number of CB non-HSCs/VSELs is inversely associated with the birth weight of preterm infants. More notably, a high number of CB HSCs is strongly associated with a lower risk of prematurity complications including intraventricular hemorrhage, respiratory distress syndrome, infections, and anemia. The number of HSCs remains stable for the first six weeks of postnatal life. Besides, the number of CSPCs in CB is significantly higher in preterm infants than in full-term neonates (p < 0.0001) and extensively decreases in preterm babies during next six weeks after birth. Finally, the growth of burst-forming unit of erythrocytes (BFU-E) and colony-forming units of granulocyte-macrophage (CFU-GM) obtained from CB of premature neonates is higher than those obtained from CB of full-term infants and strongly correlates with the number of CB-derived CSPCs.ConclusionWe conclude that CB HSCs are markedly associated with the development of premature birth complications. Thus, HSCs ought to be considered as the potential target for further research as they may be relevant for predicting and controlling the morbidity of premature infants. Moreover, the observed levels of non-HSCs/VSELs circulating in CB are inversely associated with the birth weight of preterm infants, suggesting non-HSCs/VSELs might be involved in the maturation of fetal organism.

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“…[21] However, these findings are not consistent with human studies, in which this heterogeneous population (identified by flow cytometry with the expression of CD34, CD133, VEGFR-2, CD45 and CD144 surface markers in different combinations) do not correlate with the development of BPD, neither at birth nor at some days after birth. [222324] Conversely, cord blood circulating ECFCs (i.e., EPCs of angiogenic origin, enumerated as number of colonies developing from cord blood mononuclear cells), have been shown, in two independent studies, to be lower in cord blood from infants who later develop BPD compared with infants without BPD. [2225] Although both studies suggest that loss of circulating ECFCs may be implicated in the pathogenesis of lung vascular disruption typical of BPD, none of the two studies provide a mechanistic link.…”

Section: Endothelial Progenitor Cell Depletionmentioning

confidence: 99%

Stem cell therapy for neonatal diseases associated with preterm birth

et al. 2013

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In the last decades, the prevention and treatment of neonatal respiratory distress syndrome with antenatal steroids and surfactant replacement allowed the survival of infants born at extremely low gestational ages. These extremely preterm infants are highly vulnerable to the detrimental effects of oxidative stress and infection, and are prone to develop lung and brain diseases that eventually evolve in severe sequelae: The so-called new bronchopulmonary dysplasia (BPD) and the noncystic, diffuse form of periventricular leukomalacia (PVL). Tissue simplification and developmental arrest (larger and fewer alveoli and hypomyelination in the lungs and brain, respectively) appears to be the hallmark of these emerging sequelae, while fibrosis is usually mild and contributes to a lesser extent to their pathogenesis. New data suggest that loss of stem/progenitor cell populations in the developing brain and lungs may underlie tissue simplification. These observations constitute the basis for the application of stem cell-based protocols following extremely preterm birth. Transplantation of different cell types (including, but not limited to, mesenchymal stromal cells, endothelial progenitor cells, human amnion epithelial cells) could be beneficial in preterm infants for the prevention and/or treatment of BPD, PVL and other major sequelae of prematurity. However, before this new knowledge can be translated into clinical practice, several issues still need to be addressed in preclinical in vitro and in vivo models.

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Endothelial progenitor cells, bronchopulmonary dysplasia and other short-term outcomes of extremely preterm birth

Cited by 27 publications

References 39 publications

Cord blood angiogenic progenitor cells are decreased in bronchopulmonary dysplasia

Cord blood angiogenic progenitor cells are decreased in bronchopulmonary dysplasia

Circulating hematopoietic stem cell count is a valuable predictor of prematurity complications in preterm newborns

Stem cell therapy for neonatal diseases associated with preterm birth

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