Circulation Enrichment of Functional Endothelial Progenitor Cells by Infantile Phototherapy

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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.

Section: Discussionsupporting

confidence: 86%

Endothelial Progenitor Cell Mobilization in Preterm Infants With Sepsis Is Associated With Improved Survival

Siavashi

Asadian

Taheri-Asl³

et al. 2017

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“…5 × 10 4 EPCs were seeded on the top chamber of the transwell Inserts. The bottom chamber contained 750 µL serum‐free M199 with 50 ng/mL VEGF . After incubation for 24 h in a CO 2 incubator, the bottom chamber were stained with DAPI (1 μg/mL, Cat No: D9542; Sigma‐Aldrich, St. Louis, MO) to visualize the migrated cells for counting.…”

Section: Methodsmentioning

confidence: 99%

“…Circulating EPCs in preterm infants was cultured as described previously with some modifications. 9,19 PBMNCs were isolated and seeded on fibronectin-coated plates and incubated in the M199 medium with EGM-2 Supplement Pack (Cat No: C-39211, Promocell, Heidelberg, Germany) at 37°C and 5% CO 2 . The medium was changed after three days to remove non-adherent cells.…”

Section: Cultivation Of Cepcsmentioning

confidence: 99%

“…Along with stem cells, endothelial progenitor cells (EPCs), which are able to differentiate into mature endothelial cells, play a role in tissue repair . EPCs are mobilized from the bone marrow into the circulation in response to tissue ischemia or endothelial damage, with subsequent homing to sites of injury, and participation in neovascularization . EPCs were characterized through partial expression of a variety of cell surface markers, including CD34, CD133, Tie2, and VEGF receptor 2 (KDR), and with capability of adherence to endothelium and participation in new vessel formation …”

Section: Introductionmentioning

confidence: 99%

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Increased circulation mobilization of endothelial progenitor cells in preterm infants with retinopathy of prematurity

Babaei

Alibabrdel

Asadian

et al. 2018

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Retinopathy of prematurity (ROP) is a result of increased pathological neoangiogenesis of the retina in preterm infants. Cells responsible for the pathogenesis of ROP are unclear, but some evidence indicates that bone marrow derived cells are involved in this disorder. Endothelial progenitor cells (EPCs), play a role in angiogenesis in response to tissue ischemia or endothelial damage. In this study, the number of cEPCs in preterm infants with ROP was determined to identify whether the circulation mobilization of EPCs is associated with ROP. We evaluated 99 participants in this study: 22 preterm infants with ROP, 35 preterm infants without ROP, and 42 full-term infants. The release of EPCs in the circulation was first quantified. Thereafter, cEPCs were harvested and cultivated, then the biological features of these cells including migratory, proliferative, and tubulogenic activities were analyzed. The mRNA levels of some proangiogenic factors were also measured in preterm infants. Our results showed greater numbers of cEPCs in infants with ROP, which was associated with increased serum concentrations of angiogenic factors and with augmented proliferative, migratory, and tubulogenic activity of these cells. Western blotting showed increased protein levels of VEGF and HIF-α in cEPCs harvested from ROP infants. This study showed that ROP in preterm infants is associated with increased mobilization of EPCs into the circulation. Therefore, increased cEPCs along with elevated levels of angiogenic factors and tubulogenesis suggest that these cells may play a role in the development and progression of ROP.

“…Since EPCs are described to have a great therapeutic potency to regenerate ischemic injuries by neovascularization while being a potential target for the prevention of tumor growth, these cells are the focus of many studies to define their biological features under a variety of environmental conditions [Kawamoto et al, , Zammaretti and Zisch, ; Siavashi et al, ]. Penta‐transmembrane glycoprotein prominin‐1 also called CD133 and AC133 is a stem/progenitor cell marker.…”

mentioning

confidence: 99%

β3‐Adrenergic Regulation of EPC Features Through Manipulation of the Bone Marrow MSC Niche

Vafaei

Nassiri

Siavashi

2017

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Mesenchymal stem cells (MSCs) reside in a specific niche in the bone marrow, however, biological features of this niche are still not fully understood. Given the interactions of MSCs with endothelial cells in different tissues, bone marrow MSC niche may influence the biological features of endothelial progenitor cells (EPCs). To understand the role of the sympathetic nervous system in regulation of the MSC niche, we examined whether the manipulation of the MSC niche via β3-adrenergic signals will affect EPC features. A selective β3 agonist (BRL37344) or a β3 antagonist (SR59230A) was administered in mice for 2 weeks to determine the potential effects of these regimens on the population of CD133 stem cells in the bone marrow. Then, bone marrow-derived MSCs and EPCs were harvested and expanded from the mice to examine the effect of changes in the MSC niche on EPC features. Improved MSC colony forming potency with increased bone marrow stromal cell-derived factor 1 (SDF-1) (also known as C-X-C motif chemokine 12 [CXCL12]) expression was shown as a result of intensification of the bone marrow adrenergic signals through BRL37344 injection. On the other hand, the blockage of these signals limited the expression level of SDF-1 and resulted in bone marrow enrichment of CD133 cells. Manipulation of the MSC niche and decreased SDF-1 expression via SR59230A injection also prompted EPCs to form more colonies with augmented proliferation and differentiation capacity. Overall, our results indicate that the β3-adrenergic signals regulate the MSC niche, thereby resulting in modulation of EPC biological features. J. Cell. Biochem. 118: 4753-4761, 2017. © 2017 Wiley Periodicals, Inc.