Microvascular dysfunction plays a key role in the pathology of sepsis, leading to multi-organ failure, and death. Circulating endothelial progenitor cells (cEPCs) are critically involved in the maintenance of the vascular homeostasis in both physiological and pathological contexts. In this study, concentration of cEPCs in preterm infants with sepsis was determined to recognize whether the EPC mobilization would affect the clinical outcome of infantile sepsis. One hundred and thirty-three preterm infants (81 with sepsis and 52 without sepsis) were enrolled in this study. The release of EPCs in circulation was first quantified. Thereafter, these cells were cultivated and biological features of these cells such as, proliferation and colony forming efficiency were analyzed. The levels of chemoattractant cytokines were also measured in infants. In mouse models of sepsis, effects of VEGF and SDF-1 as well as anti-VEGF and anti-SDF-1 were evaluated in order to shed light upon the role which the EPC mobilization plays in the overall survival of septic animals. Circulating EPCs were significantly higher in preterm infants with sepsis than in the non-sepsis group. Serum levels of VEGF, SDF-1, and Angiopoietin-2 were also higher in preterm infants with sepsis than in control non-sepsis. In the animal experiments, injection of VEGF and SDF-1 prompted the mobilization of EPCs, leading to an improvement in survival whereas injection of anti-VEGF and anti-SDF-1 was associated with significant deterioration of survival. Overall, our results demonstrated the beneficial effects of EPC release in preterm infants with sepsis, with increased mobilization of these cells was associated with improved survival. J. Cell. Biochem. 118: 3299-3307, 2017. © 2017 Wiley Periodicals, Inc.
Angiogenesis is a regulated process involving the proliferation, migration, and remodeling of different cell types particularly mature endothelial cells and recently discovered progenitor cells, named as endothelial progenitor cells (EPCs). Up to now, many attempts have been made to understand the dynamic balance of pro-and anti-angiogenic factors on EPCs on different milieu. It has been accepted that Ang-1, -2 and Tie-1, -2 signaling play a key role on angiogenesis pathways in endothelial lineage cells. In the current experiment, the angiogenic/angiomodulatory potency of Ang-1 and -2 was investigated on isolated EPCs. Freshly isolated EPCs were exposed to different concentrations of Ang-1 and -2 (25 and 50 ng/ml) over a course of 7 and 14 days. Corroborating to our results, a superior effect of Ang-1 on angiogenic properties, including an increased concentration of vascular endothelial growth factor, in vitro tubulogenesis, EPC migratory, Tie-2 expression and clonogenicity, was determined. A large amount of positive mature endothelium markers was achieved in EPCs being-exposed to Ang-1 peptide. Nonetheless, the number of CD133 positive cells increased in the presence of Ang-2. Collectively, we conclude that Ang-1 potentially induces functional and mature vascular-like behavior in EPCs more than Ang-2.ARTICLE HISTORY
Phototherapy is the most common therapy used for severe jaundice. There is increasing evidence that phototherapy can directly affect the expression and function of cell surface receptors including adhesion molecules, cytokines, and growth factor receptors. In this study, the effect of two infantile phototherapy regimens, including single and intensive phototherapy was investigated on biological features of circulation endothelial progenitor cells (cEPCs), as well as on serum secretion of two important chemotactic cytokines, SDF-1 and VEGF. Sixty infants diagnosed with severe hyperbilirubinemia and exposed to phototherapy were enrolled in this study. cEPCs were isolated before and after phototherapy and then migratory, proliferative, tubulogenic, and functional properties of these cells were analyzed. Our results revealed that intensive phototherapy markedly increased the release of EPCs into the circulation, and augmented the serum concentrations of both SDF-1 and VEGF cytokines. Cell proliferation, tubulogenic, and migratory properties of cEPCs isolated and expanded from infants with intensive phototherapy were significantly improved. cEPCs from infants with intensive phototherapy also showed greater levels of acetylated low-density lipoprotein and lectin binding. Overall, our results showed that the intensive phototherapy regimen can mobilize functional EPCs into the circulation through up-regulation of serum levels of VEGF and SDF-1, indicating phototherapy as an effective modality for improvement of stem cell mobilization in the therapeutic regenerative medicine. J. Cell. Biochem. 118: 330-340, 2017. © 2016 Wiley Periodicals, Inc.
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