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

Abstract

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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“…11 Recently, we reported that the increased number of hematopoietic SCs (CD45 + lin-CD184 + ) circulating in CB is strongly associated with a lower risk of developing premature birth complications, including intraventricular hemorrhage, respiratory distress syndrome, infections, and anemia. 12 Furthermore, we observed that con centrations of a more immature, nonhematopoietic SC of the CD45-lin-CD184 + phenotype in CB are inversely associated with birth weight in preterm infants, suggesting that these cells might be involved in the maturation of the fetus. 12 We also observed that the relative number of circulating endothelial progenitor cells in CB was inversely associated with Apgar scores of preterm infants.…”

“…12 Furthermore, we observed that con centrations of a more immature, nonhematopoietic SC of the CD45-lin-CD184 + phenotype in CB are inversely associated with birth weight in preterm infants, suggesting that these cells might be involved in the maturation of the fetus. 12 We also observed that the relative number of circulating endothelial progenitor cells in CB was inversely associated with Apgar scores of preterm infants. A positive association between the number of endothelial progenitor cells with "early" phenotype (CD133 + /CD34 + /CD144 + ) and the risk of respiratory distress syndrome, retinopathy of prematurity, bronchopulmonary dysplasia, and infections was found; however, multivariate analyses revealed that an increase in endothelial progenitor cells was not an independent predictor of prematurity complications but was directly related to lower gestational age.…”

“…In our previous studies, we reported that specific SPC types, such as hematopoietic SCs, nonhematopoietic SCs, and endothelial progenitor cells circulating in CB, are markedly associated with the development of premature birth complications. 12,13 To our knowledge, the present study is the first to document and assess autologous CB transfusion performed soon after birth in relation to the frequency of different outcomes from prematurity-related complications. We reported here for the first time that only 40% of premature CB recipients, compared with 67% of newborns in the control group, developed neurologic complications in the form of intraventricular hemorrhage, indicating that autologous CB may have the potential to reduce the rate of prematurity complications, mostly related to neurodevelopmental processes.…”

“…20 Furthermore, as we recently reported, the number of different SPCs circulating in CB has been associated with the development of premature birth complications. 12 Therefore, it has been hypothesized that the restoration of homeostasis could be possible if the different SPCs lost during premature delivery are reinfused after birth. The use of autologous CB for the treatment of anemic newborns has long been discussed.…”

Stem Cell Therapies in Neonatology

“…It will be further highlighted information on novel therapeutic approach proposed by our group to build a basis for a potential discussion of the future clinical trials. turity (ROP), respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), necritizing enterocolitis (NEC), infections, and anemia, among others [5]. The etiology of these complications is multifactorial and includes a local and general hypoxic state, organ ischemia, and a broad-spectrum lack of adaptation to the extrauterine environment [5].…”