Circulating Endothelial Progenitor Cells in Preterm Infants with Bronchopulmonary Dysplasia

Borghesi, A.; Massa, Margherita; Campanelli, Rita; Bollani, Lina; Tzialla, Chryssoula; Figar, Tiziana; Ferrari, Giovanna; Bonetti, Elisa; Chiesa, Gaia; Silvestri, Annalisa De; Spinillo, Arsenio; Rosti, Vittorio; Stronati, Mauro

doi:10.1164/rccm.200812-1949oc

Cited by 130 publications

(136 citation statements)

References 21 publications

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“…In addition, human fetal lung ECFC and newborn rat ECFC function are also impaired after high oxygen exposure (mimicking preterm birth conditions) 36. EPC dysfunction in preterm cord blood, particularly the ECFC, has been associated with the development of BPD 56, 57. BPD is characterized by disrupted alveolar and lung vasculogenesis, and is considered an early manifestation of an impaired angiogenic capacity in preterm newborns 26.…”

Section: Discussionmentioning

confidence: 99%

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

Bertagnolli

Xie

Paquette

et al. 2018

JAHA

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BackgroundPreterm birth is linked to cardiovascular risks and diseases. Endothelial progenitor cells play a critical role in vascular development and repair. Cord blood endothelial progenitor cells of preterm‐born infants, especially endothelial colony‐forming cells (ECFC), show enhanced susceptibility to prematurity‐related pro‐oxidant stress. Whether ECFC dysfunction is present in adulthood following preterm birth is unknown.Methods and ResultsThis cross‐sectional observational study includes 55 preterm‐born (≤29 gestational weeks) young adults (18–29 years old, 38% male) and 55 sex‐ and age‐matched full‐term controls. ECFC were isolated from peripheral blood; cell proliferative and vascular cord formation capacities were assessed in vitro. Daytime systolic blood pressure was higher, whereas glucose tolerance and body mass index were lower in preterm‐born subjects. ECFC colonies grew in culture for 62% of full‐term‐ and 58% of preterm‐born participants. Preterm‐born participants have formed ECFC colonies later in culture and have reduced proliferation compared with controls. Only in preterm‐born individuals, we observed that the later the ECFC colony grows in culture, the worse was overall ECFC function. In addition, in preterms, elevated systolic blood pressure significantly correlated with reduced ECFC proliferation (rS=−0.463; P=0.030) and numbers of branches formed on matrigel (rS=−0.443; P=0.039). In preterm‐born subjects, bronchopulmonary dysplasia was associated with impaired ECFC function, whereas exposure to antenatal steroids related to better ECFC function.ConclusionsThis study is the first to examine ECFC in preterm‐born adults and to demonstrate ECFC dysfunction compared with full‐term controls. In the preterm‐born group, ECFC dysfunction was associated with bronchopulmonary dysplasia, the major prematurity‐related neonatal morbidity, and with increased systolic blood pressure into adulthood.

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Section: Discussionmentioning

confidence: 99%

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

Bertagnolli

Xie

Paquette

et al. 2018

JAHA

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“…In one study, ECFC colony count was decreased in infants with decreasing gestational age [5]. In another study, Baker et al found the opposite -preterm cord blood had a higher ECFC colony count and growth rate compared to term cord blood [23].…”

Section: Endothelial Colony Forming Cells (Ecfcs) and Bpdmentioning

confidence: 96%

“…Two studies have shown that ECFCs are decreased in cord blood samples of preterm infants who subsequently develop BPD as compared to preterm infants with mild or no BPD [5,23]. These assays were done using cord blood taken at birth before exposure of the infants to postnatal stress and before they developed BPD and so represent a predisposition to illness as opposed to a reaction to a biological challenge.…”

Section: Endothelial Colony Forming Cells (Ecfcs) and Bpdmentioning

confidence: 99%

“…In addition, low levels of bone marrow-derived and circulating endothelial progenitors have been observed in the blood of hyperoxia exposed neonatal mice [4] that develop BPD, suggesting that bone marrow-derived endothelial progenitors may play a role in neonatal lung development. A human study reported lower levels of endothelial colony forming cells (ECFC) in cord blood from preterm infants who developed BPD than in cord blood from preterm infants who did not develop BPD [5]. However, others have observed higher or equivalent numbers of ECFC counts in cord blood from preterm deliveries as compared to term cord blood [6,7].…”

Section: Introductionmentioning

confidence: 99%

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Circulating Endothelial Progenitors and Bone Marrow Derived Cells as Biomarkers for Risk of Bronchopulmonary Dysplasia

Kirzner¹

2014

J Bone Marrow Res

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Bronchopulmonary dysplasia (BPD), also known as neonatal chronic lung disease, is a multifactorial disease and its pathogenesis starts even before birth. Animal models of BPD and the study of infants with BPD suggest that impaired lung vascular development leads to the failure of alveolar development and strategies that promote vascular development result in improved alveolarization of the lung. Since 1997 when Asahara identified endothelial cell progenitors (EPCs) as blood cells having the ability to contribute to postnatal vasculogenesis, several studies have attempted to elucidate the role of EPCs in neonatal lung development and lung injury and repair. This review outlines the progress in defining early EPCs (believed to be of hematopoietic origin) and late EPCs or true EPCs (believed to be of endothelial origin) through the use of cell culture assays and flow cytometric characterization. Both animal and human studies have attempted to correlate the frequency of these specific populations with susceptibility to BPD. Animal studies use hyperoxia or endotoxininduced lung injury as a model of BPD. Human studies use frequencies of specific cell populations as a prognostic index of BPD. Conflicting outcomes are likely the result of a lack of consistent definitions. Recently, there is increasing evidence that blood and bone marrow-derived stem cells exert a beneficial effect in models of chronic lung injury, not so much by engraftment and differentiation, but by a paracrine effect on the existing lung progenitor cells.

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“…EPCs is one of the key cells mediating vascular growth, which can mobilize from bone marrow and home to the site of vascular injuries, promoting neovascularization (5). There is data showing that reduced numbers or dysfunction of EPCs at birth is associated with the development of BPD (6,7). In addition, a reduction in the number of EPCs in the bone marrow, circulation and lungs has also emerged in animal models of BPD (8).…”

mentioning

confidence: 99%

Combined iNO and endothelial progenitor cells improve lung alveolar and vascular structure in neonatal rats exposed to prolonged hyperoxia

Sun

Qian

2015

Pediatr Res

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Background: Stem cells or inhaled nitric oxide (iNO) are reported to improve lung structures in bronchopulmonary dysplasia (BPD) models. We hypothesized that combined iNO and transplanted endothelial progenitor cells (EPCs) might restore lung structure in rats after neonatal hyperoxia. Methods: Litters were separated into eight groups: room air, hyperoxia, hyperoxia + iNO, hyperoxia + iNO + L-NAME, hyperoxia + EPCs, hyperoxia + EPCs + L-NAME, hyperoxia + EPCs + iNO, and hyperoxia + EPCs + iNO + L-NAME. Litters were exposed to hyperoxia from the 21st day, then, sacrificed. EPCs were injected on the 21st day. L-NAME was injected daily for 7 d from the 21st day. Serum vascular endothelial growth factor (VEGF), radial alveolar count (RAC), VIII factor, EPCs engraftment, lung VEGF, VEGFR2, endothelial nitric oxide (eNOS) and SDF-1 expression, and NO production were examined. results: Hyperoxia exposure led to air space enlargement, loss of lung capillaries, and low expression of VEGF and eNOS. Transplanted EPCs, when combined with iNO, had significantly increased engraftment in lungs, compared to EPCs alone, upon hyperoxia exposure. There was improvement in alveolarization, microvessel density, and upregulation of VEGF and eNOS proteins in the hyperoxia-exposed EPCs with iNO group, compared to hyperoxia alone. conclusion: Combined EPCs and iNO improved lung structures after neonatal hyperoxia. This was associated with the upregulation of VEGF and eNOS expression.B ronchopulmonary dysplasia (BPD) is a chronic lung disease associated with significant mortality and morbidity in premature infants. New BPD is characterized by arrested alveolar and vascular growth (vascular hypothesis of BPD) (1,2). Alveolar formation is a highly coordinated process between the development of airways and pulmonary vasculature (3). Exposure to inflammation caused by excessive O 2 supplementation is hypothesized to interfere with the coordinated process of normal human lung development. Neonatal hyperoxia exposure is known to disrupt alveolar formation and growth, providing a useful model for studying BPD (4).Cell-based therapy is a novel approach that offers much promise in the prevention and treatment of BPD, including embryonic stem cells, mesenchymal stem cells, placental stem cells, umbilical cord stem cells, amniotic fluid and amnionderived cells, and lung progenitor cells. Endothelial progenitor cells (EPCs) are precursors of endothelial cells, which have the capacity of self-renewal and proliferation. EPCs is one of the key cells mediating vascular growth, which can mobilize from bone marrow and home to the site of vascular injuries, promoting neovascularization (5). There is data showing that reduced numbers or dysfunction of EPCs at birth is associated with the development of BPD (6,7). In addition, a reduction in the number of EPCs in the bone marrow, circulation and lungs has also emerged in animal models of BPD (8). Evidences that angiogenic cells treatment can restore lung structure have been demonstrated. Balasubramaniam et al...

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Circulating Endothelial Progenitor Cells in Preterm Infants with Bronchopulmonary Dysplasia

Cited by 130 publications

References 21 publications

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

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

Circulating Endothelial Progenitors and Bone Marrow Derived Cells as Biomarkers for Risk of Bronchopulmonary Dysplasia

Combined iNO and endothelial progenitor cells improve lung alveolar and vascular structure in neonatal rats exposed to prolonged hyperoxia

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