title: Mobilization of circulating progenitor cells following brain injury in premature neonates could be indicative of an endogenous repair process. A pilot study.
abstract: BACKGROUND
  Preclinical data and adult studies have showed an endogenous regeneration process following brain damage that involves mobilization of progenitor cells. This process is not well described in preterm neonates. The present study aims to investigate the mobilization of Circulating Progenitor Cells (CPCs) and their relation to biomarkers of brain injury in preterm neonates.
  
  
  METHODS
  This is a prospective cohort study of preterm infants with gestational age (GA) <34 weeks. Serial cranial ultrasounds scans were performed in all neonates. Brain injury was defined by the presence of intraventricular hemorrhage grade III/IV, cystic periventricular leukomalacia or infarct. Peripheral blood samples were collected from all neonates on days(d) 1, 3, 9, 18 and 45 of life for the measurement of levels of CPCs [early and late Endothelial Progenitor Cells (EPCs), Haematopoietic Stem Cells (HSCs) and Very Small Embryonic-Like Stem Cells (VSELs)], Neuron-Specific Enolase (NSE), S100b, Erythropoietin (EPO) and Stromal Cell-Derived Factor-1 (SDF-1) .
  
  
  RESULTS
  Ten out of the 23 preterm infants included in the study developed brain injury; the remaining thirteen infants served as controls. In the brain injury group a significant increase of HSCs (d9, d45), early EPCs (d3, d9, d18) and late EPCs (d1, d3, d9, d18, d45) was observed compared to controls. VSELs on d45 were significantly higher in controls. S100b on d1, EPO on d1, SDF-1 on d3 and NSE on d18 were significantly increased in the brain injury group. Moreover, CPCs were significantly related to S100b, NSE, EPO and SDF-1 levels at multiple time points.
  
  
  CONCLUSIONS
  The observed pattern of CPCs mobilization and its association with biomarkers following brain injury in preterm neonates indicate the existence of an endogenous brain regeneration process. Enhancement of this process with exogenous progenitor cell transplantation might be a powerful therapeutic strategy to restore brain damage and improve the neurodevelopmental outcome in premature infants. Hippokratia 2015; 19 (2):141-147.
authors.affiliation: 1 Neonatal Department and NICU, Hippokration General Hospital, Aristotle University of Thessaloniki, Greece.
authors.forename: N
authors.initials: N
authors.lastname: Efstathiou
authors.affiliation: 1 Neonatal Department and NICU, Hippokration General Hospital, Aristotle University of Thessaloniki, Greece.
authors.forename: V
authors.initials: V
authors.lastname: Soubasi
authors.affiliation: Biochemistry Department, Medical School, Aristotle University of Thessaloniki, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Koliakos
authors.affiliation: Immunology Laboratory, Pulmonology Department, Papanikolaou General Hospital, Aristotle University of Thessaloniki, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Kyriazis
authors.affiliation: 1 Paediatric Department, Hippokration General Hospital, Aristotle University of Thessaloniki, Greece.
authors.forename: D I
authors.initials: DI
authors.lastname: Zafeiriou
authors.affiliation: Biochemistry Department, Hippokration General Hospital, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Slavakis
authors.affiliation: 1 Neonatal Department and NICU, Hippokration General Hospital, Aristotle University of Thessaloniki, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Kantziou
authors.affiliation: Medical school, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: T
authors.initials: T
authors.lastname: Pozotou
authors.affiliation: Immunology Laboratory, Pulmonology Department, Papanikolaou General Hospital, Aristotle University of Thessaloniki, Greece.
authors.forename: O
authors.initials: O
authors.lastname: Chatzizisi
authors.affiliation: 1 Neonatal Department and NICU, Hippokration General Hospital, Aristotle University of Thessaloniki, Greece.
authors.forename: V
authors.initials: V
authors.lastname: Drosou-Agakidou
keywords: Preterm; brain injury; neonates; progenitor cells