Effect of VEGF/GREDVY Modified Surface on Vascular Cells Behavior

We synthesized B-He/B-GREDVY and immobilized them on avidin-coated surfaces.To examine the immobilization of molecules in the material, the following experiments were performed:fluorescein isothiocyanate(FITC) fluorescence staining, water contact angle and atomic force microscopy(AFM) measurements. Besides, the biological evaluation experiments were also performed, such as platelets adhesion and activation, the culturing of smooth muscle cells(SMC) and endothelial cells(EC). These experimental results show that the modified surfaces could prevent the hyperproliferation of SMC, and promote the proliferation and migration of EC and EPC. Furthermore, the adding of VEGF improved the EC adhesion in a dynamic environment. Generally, it is expected that the modified surfaces could be used to accelerate the formation of the newly endothelial layer for the construction of platforms for coronary artery stent therapy.

Transplantation of endothelial progenitor cells transfected with VEGF165 to restore erectile function in diabetic rats

The present study investigated the effect of transplanting endothelial progenitor cells （EPCs） transfected with the vascular endothelial growth factor gene （VEGF165） into the corpora cavernosa of rats with diabetic erectile dysfunction （ED）. A rat model of diabetic ED was constructed via intraperitoneal injection of streptozotocin. After streptozotocin treatment, pre-treated EPCs from each of three groups of rats were transplanted into their corpora cavernosa. Our results, following intracavernosal pressure （ICP） monitoring, showed that ICP increased significantly among rats in the trial group when compared to the results from rats in the blank-plasmid and control groups during basal conditions and electrical stimulation （P〈O.01 for both comparisons）. Histological examination revealed extensive neovascularisation in the corpora cavernosa of rats in the trial group. Fluorescence microscopy indicated that many of the transplanted EPCs in the trial group survived, differentiated into endothelial cells and integrated into the sites of neovascularisation. Based on the results of this study, we conclude that transplantation of VEGF165-transfected EPCs into the corpora cavernosa of rats with diabetic ED restores erectile function.

Endothelial progenitor cells, potential biomarkers for diagnosis and prognosis of ischemic stroke: protocol for an observational case-control study

Ischemic stroke is a devastating,life altering event which can severely reduce patient quality of life.Despite years of research there have been minimal therapeutic advances.Endothelial progenitor cells(EPCs),stem cells involved in both vasculogenesis and angiogenesis,may be a potential therapeutic target.After a stroke,EPCs migrate to the site of ischemic injury to repair cerebrovascular damage,and their numbers and functional capacity may determine patients'outcome.This study aims to determine whether the number of circulating EPCs and their functional aspects may be used as biomarkers to identify the type(cortical or lacunar)and/or severity of ischemic stroke.The study will also investigate if there are any differences in these characteristics between healthy volunteers over and under 65 years of age.100 stroke patients(50 lacunar and 50 cortical strokes)will be recruited in this prospective,observational case-controlled study.Blood samples will be taken from stroke patients at baseline(within 48 hours of stroke)and days 7,30 and90.EPCs will be counted with flow cytometry.The plasma levels of pro-and anti-angiogenic factors and inflammatory cytokines will also be determined.Outgrowth endothelial cells will be cultured to be used in tube formation,migration and proliferation functional assays.Primary outcome is disability or dependence on day 90 after stroke,assessed by the modified Rankin Scale.Secondary outcomes are changes in circulating EPC numbers and/or functional capacity between patient and healthy volunteers,between patient subgroups and between elderly and young healthy volunteers.Recruitment started in February 2017,167 participants have been recruited.Recruitment will end in November 2019.West Midlands-Coventry&Warwickshire Research Ethics Committee approved this study(REC number:16/WM/0304)on September8,2016.Protocol version:2.0.The Bayraktutan Dunhill Medical Trust EPC Study was registered in ClinicalTrials.gov(NCT02980354)on November 15,2016.This study will determine whether the number of EPCs can be used as a prognostic or diagnostic marker for ischemic strokes and is a step towards discovering if transplantation of EPCs may aid patient recovery.

Angiotensin Ⅱ promotes NO production, inhibits apoptosis and enhances adhesion potential of bone marrow-derived endothelial progenitor cells

Endothelial progenitor cells （EPCs） participate in the processes of postnatal neovascularization and re-endothelialization in response to tissue ischemia and endothelial injury. The level of EPCs present has been found to be directly associated with the outcome of cardiovascular diseases, and could be regulated by stimulatory or inhibitory factors. Given the close relationship between angiotensin Ⅱ （AngⅡ） and the cardiovascular＇ system, we investigated the effect of AngⅡ on the activities of bone marrow （BM）-derived EPCs. Cells were isolated from BM of rats by density gradient centrifugation. Administration of AngⅡ significantly promoted nitric oxide （NO） release, inhibited EPC apoptosis and enhanced EPC adhesion potential. All of these AngⅡ-mediated effects on EPCs were attenuated by pretreatment with valsartan or L-NAME. Moreover, both LY294002 and wortmannin abolished the anti-apoptotic effect of AngⅡ. Western blot analyses indicated that endothelial NO synthase （eNOS） protein and phosphorylated Akt increased with the treatment of AngⅡ in EPCs. Thus, AngⅡ improved several activities of EPCs through AngⅡ type 1 receptor （AT1R）, which may represent a possible mechanism linking AnglI and ATIR with angiogenesis. Additionally, AngⅡ-induced NO synthesis through eNOS in EPCs regulates apoptosis and adhesion, and the PI3-kinase/Akt pathway has an essential role in AngⅡ-induced antiapoptosis signaling.

Growth factor- and cytokine-stimulated endothelial progenitor cells in post-ischemic cerebral neovascularization

Endothelial progenitor cells are resident in the bone marrow blood sinusoids and circulate in the peripheral circulation. They mobilize from the bone marrow after vascular injury and home to the site of injury where they differentiate into endothelial cells. Activation and mobilization of endothelial progenitor cells from the bone marrow is induced via the production and release of endothelial progenitor cell-activating factors and includes specific growth factors and cytokines in response to peripheral tissue hypoxia such as after acute ischemic stroke or trauma. Endotheli- al progenitor cells migrate and home to specific sites following ischemic stroke via growth factor/ cytokine gradients. Some growth factors are less stable under acidic conditions of tissue isch- emia, and synthetic analogues that are stable at low pH may provide a more effective therapeutic approach for inducing endothelial progenitor cell mobilization and promoting cerebral neovascularization following ischemic stroke.

Endothelial progenitor cells in peripheral blood may serve as a biological marker to predict severe acute pancreatitis

AIM To investigate the significance of endothelial progenitor cells (EPCs) in predicting severe acute pancreatitis (SAP). METHODS We recruited 71 patients with acute pancreatitis (AP) and excluded 11 of them; finally, cases of mild acute pancreatitis (MAP) (n = 30) and SAP (n = 30), and healthy volunteers (n = 20) were internalized to investigate levels of EPCs, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), fibrinogen (FIB) and white blood cells (WBC) in peripheral blood. RESULTS The levels of TNF-alpha, WBC, FIB and CRP were higher both in SAP and MAP cases than in healthy volunteers (P < 0.05, all). Interestingly, the level of EPCs was higher in SAP than MAP (1.63% +/- 1.47% vs 6.61% +/- 4.28%, P < 0.01), but there was no significant difference between the MAP cases and healthy volunteers (1.63% +/- 1.47% vs 0.55% +/- 0.54%, P > 0.05). Receiver operating characteristics curve (ROC) showed that EPCs, TNF-alpha, CRP and FIB were significantly associated with SAP, especially EPCs and CRP were optimal predictive markers of SAP. When the cut-off point for EPCs and CRP were 2.26% and 5.94 mg/dL, the sensitivities were 90.0% and 73.3%, and the specificities were 83.3% and 96.7%. Although, CRP had the highest specificity, and EPCs had the highest sensitivity and highest area under the curve value (0.93). CONCLUSION Data suggest that EPCs may be a new biological marker in predicting SAP.

The secretome of endothelial progenitor cells: a potential therapeutic strategy for ischemic stroke

Ischemic stroke continues to be a leading cause of mortality and morbidity in the world. Despite recent advances in the field of stroke medicine, thrombolysis with recombinant tissue plasminogen activator remains as the only pharmacological therapy for stroke patients. However, due to short therapeutic window(4.5 hours of stroke onset) and increased risk of hemorrhage beyond this point, each year globally less than 1% of stroke patients receive this therapy which necessitate the discovery of safe and efficacious therapeutics that can be used beyond the acute phase of stroke. Accumulating evidence indicates that endothelial progenitor cells(EPCs), equipped with an inherent capacity to migrate, proliferate and differentiate, may be one such therapeutics. However, the limited availability of EPCs in peripheral blood and early senescence of few isolated cells in culture conditions adversely affect their application as effective therapeutics. Given that much of the EPC-mediated reparative effects on neurovasculature is realized by a wide range of biologically active substances released by these cells, it is possible that EPC-secretome may serve as an important therapeutic after an ischemic stroke. In light of this assumption, this review paper firstly discusses the main constituents of EPC-secretome that may exert the beneficial effects of EPCs on neurovasculature, and then reviews the currently scant literature that focuses on its therapeutic capacity.

Adult endothelial progenitor cells from human peripheral blood maintain monocyte/macrophage function throughout in vitro culture

Mononuclear cells （MNCs） isolated from peripheral blood by density gradient centrifugation were plated on human fibronectin-coated culture plates and cultured in EGM-2 medium. Attached spindle-shaped cells, reported as endothelial progenitor cells （EPCs） by some investigators, had elongated from adherent round cells, but had not proliferated from a small number of cells as supposed previously. The growth curve of the primary EPCs showed that the cells had little proliferative capacity. Flow cytometry analysis showed that the cells could express some of the endothelial lineage markers, while they could also express CD 14, which is considered a marker of monocyte/macrophage lineages throughout culture. In endothelial function assays, the cells demonstrated a lower level of expression of eNOS than mature endothelial cells in the reverse transcription-polymerase chain reaction and did not show an ability to develop tube-like structures in angiogenesis assay in vitro. In this study, we identified the monocytoid function of EPCs by the combined Dillabeled acetylated low-density lipoprotein （Dil-Ac-LDL） and Indian ink uptake tests. All the cells were double positive for Dil- Ac-LDL and Indian ink uptake at days 4, 14 and 28 of culture, which means the EPCs maintained monocytoid function throughout the culture. Therefore, although adult EPCs from peripheral MNCs have some endothelial lineage properties, they maintain typical monocytic function and have little proliferative capacity.

Endothelial precursor cells promote angiogenesis in hepatocellular carcinoma

AIM:To investigate the role of bone marrow-derived endothelial progenitor cells(EPCs) in the angiogenesis of hepatocellular carcinoma(HCC).METHODS:The bone marrow of HCC mice was reconstructed by transplanting green fluorescent protein(GFP) + bone marrow cells.The concentration of circulating EPCs was determined by colony-forming assays and fluorescence-activated cell sorting.Serum and tissue levels of vascular endothelial growth factor(VEGF) and colony-stimulating factor(CSF) were quantified by enzyme-linked immunosorbent assay.The distribution of EPCs in tumor and tumor-free tissues was detected by immunohistochemistry and real-time polymerase chain reaction.The incorporation of EPCs into hepatic vessels was examined by immunofluorescence and immunohistochemistry.The proportion of EPCs in vessels was then calculated.RESULTS:The HCC model was successful established.The flow cytometry analysis showed the mean percentage of CD133CD34 and CD133VEGFR2 double positive cells in HCC mice was 0.45% ± 0.16% and 0.20% ± 0.09% respectively.These values are much higher than in the sham-operation group(0.11% ± 0.13%,0.05% ± 0.11%,n = 9) at 14 d after modeling.At 21 d,the mean percentage of circulating CD133CD34 and CD133VEGFR2 cells is 0.23% ± 0.19%,0.25% ± 0.15% in HCC model vs 0.05% ± 0.04%,0.12% ± 0.11% in control.Compared to the transient increase observed in controls,the higher level of circulating EPCs were induced by HCC.In addition,the level of serum VEGF and CSF increased gradually in HCC,reaching its peak 14 d after modeling,then slowly decreased.Consecutive sections stained for the CD133 and CD34 antigens showed that the CD133+ and CD34+ VEGFR2 cells were mostly recruited to HCC tissue and concentrated in tumor microvessels.Under fluorescence microscopy,the bone-marrow(BM)-derived cells labeled with GFP were concentrated in the same area.The relative levels of CD133 and CD34 gene expression were elevated in tumors,around 5.0 and 3.8 times that of the tumor free area.In frozen liver sections from HCC mice,cells co-expressing CD133 and VEGFR2 were identified by immunohistochemical staining using anti-CD133 and VEGFR2 antibodies.In tumor tissue,the double-positive cells were incorporated into vessel walls.In immunofluorescent staining.These CD31 and GFP double positive cells are direct evidence that tumor vascular endothelial cells(VECs) come partly from BM-derived EPCs.The proportion of GFP CD31 double positive VECs(out of all VECs) on day 21 was around 35.3% ± 21.2%.This is much higher than the value recorded on day 7 group(17.1% ± 8.9%).The expression of intercellular adhesion molecule 1,vascular adhesion molecule 1,and VEGF was higher in tumor areas than in tumor-free tissues.CONCLUSION:Mobilized EPCs were found to participate in tumor vasculogenesis of HCC.Inhibiting EPC mobilization or recruitment to tumor tissue may be an efficient strategy for treating HCC.

Apelin and vascular endothelial growth factor are associated with mobilization of endothelial progenitor cells after acute myocardial infarction

This study was designed to determine the levels of early endothelial progenitor cells （EPCs）, apelin, vascu- lar endothelial growth factor （VEGF） and stromal cell-derived growth factor-1 （SDF-1） after acute myocardial infarction （AMI）, and to investigate the relationships between these cytokines and early EPCs. Early EPCs, de- fined as CD133＋, KDR＋, and CD34~ cells, were quantified by flow cytometry. The levels of early EPCs and those cytokines in AMI patients were significantly different from those with coronary artery disease or controls （P 〈 0.05）. Plasma apelin levels were inversely correlated with Gensini score and early EPCs （both P 〈 0.01）. Early EPCs, VEGF and SDF-1 showed different patterns of changes in AMI patients during the first 24 h. The trend in the change of early EPCs was proportionally correlated with that of VEGF （P 〈 0.05）. AMI patients exhibited in- creased early EPCs with remarkably decreased apelin levels and enhanced VEGF levels.

Mobilisation of endothelial progenitor cells： one of the possible mechanisms involved in the chronic administration of melatonin preventing erectile dysfunction in diabetic rats

Diabetes-induced oxidative stress plays a critical role in the mobilisation of endothelial progenitor cells （EPCs） from the bone marrow to the circulation. This study was designed to explore the effects of chronic melatonin administration on the promotion of the mobilisation of EPCs and on the preservation of erectile function in type I diabetic rats. Melatonin was administered to streptozotocin-induced type I diabetic rats. EPCs levels were determined using flow cytometry. Oxidative stress in the bone marrow was indicated by the levels of superoxide dismutase and malondialdehyde. Erectile function was evaluated by measuring the intracavernous pressure during an electrostimulation of the cavernous nerve. The density of the endothelium and the proportions of smooth muscle and collagen in the corpus cavernosum were determined by immunohistochemistry. The administration of melatonin increased the superoxide dismutase level and decreased the malondialdehyde level in the bone marrow. This effect was accompanied by an increased level of circulating EPCs in the diabetic rats. The intracavernous pressure to mean arterial pressure ratio of the rats in the treatment group was significantly greater, compared with diabetic control rats. The histological analysis demonstrated an increase in the endothelial density of the corpus cavernosum after the administration of melatonin. However, melatonin treatment did not change the proportions of smooth muscle and collagen in the corpus cavernosum of diabetic rats. Chronic administration of melatonin has a beneficial effect on preventing erectile dysfunction （ED） in type I diabetic rats. Promoting the mobilisation of EPCs is one of the possible mechanisms involved in the improvement of ED.

Changes in Number and Biological Function of Endothelial Progenitor Cells in Hypertension Disorder Complicating Pregnancy

To examine the changes in number and function of endothelial progenitor cells （EPCs） from peripheral blood （PB） in hypertension disorder complicating pregnancy （HDCP）, 20 women with HDCP and 20 normal pregnant women at the third trimester were studied. Mononuclear cells （MNCs） from PB were isolated by Ficoll density gradient centrifugation. EPCs were identified by positive expression of both CD34 and CD133 under fluorescence microscope and positive expression of factor Ⅷ as shown by immunocytochemistry. The number of EPCs was flow-cytometrically determined. Proliferation and migration of EPCs were measured by MTT assay and modified Boyden chamber assay, respectively. The adhesion activity of EPCs was detected by counting the number of the adherent cells. The results showed that, compared with normal pregnant women, the number of EPCs was significantly reduced in HDCP （4.29%±1.21% vs 15.32%±2.00%, P〈0.01）, the functional activity of EPCs in HDCP, such as proliferation （13.45%±1.68% vs 18.45%±1.67%）, migration （37.25±7.28 cells/field vs 67.10±9.55 cells/field） and adhesion activity （20.65±5.19 cells/field vs 34.40±6.72 cells/filed） was impaired （P〈0.01）. It is concluded that the number and function of EPCs are significantly decreased in HDCP.

Endothelial progenitor cells as a therapeutic option in intracerebral hemorrhage

Intracerebral hemorrhage （ICH） is the most severe cerebrovascular disease, which represents a leading cause of death and disability in developed countries. However, therapeutic options are limited, so is mandatory to investigate repairing processes after stroke in order to develop new therapeutic strategies able to promote brain repair processes. Therapeutic angiogenesis and vasculogenesis hold promise to improve outcome of ICH patients. In this regard, circulating endothelial progenitor cells （EPCs） have recently been suggested to be a marker of vascular risk and endothelial function. Moreover, EPC levels have been associated with good neurological and functional outcome as well as reduced residual hematoma volume in ICH patients. Finally, experimental and clinical studies indicate that EPC might mediate endothelial cell regeneration and neovascularization. Therefore, EPC-based therapy could be an excellent therapeutic option in ICH. In this mini-review, we discuss the present status of knowledge about the possible therapeutic role of EPCs in ICH, molecular mechanisms, and the future perspectives and strategies for their use in clinical practice.

Erythropoietin Receptor Positive Circulating Progenitor Cells and Endothelial Progenitor Cells in Patients with Different Stages of Diabetic Retinopathy

Objective To investigate the possible involvement of erythropoietin （EPO）/erythropoietin receptor （EPOR） system in neovascularization and vascular regeneration in diabetic retinopathy （DR）. Methods EPOR positive circulating progenitor cells （CPCs： CD34^＋） and endothelial progenitor cells （EPCs： CD34^＋KDR^＋） were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients without diabetes （n=7）, non-prolif- erative DR （NPDR, n=7）, proliferative DR （PDR, n=8）, and PDR complicated with diabetic nephropathy （PDR-DN, n=7）. Results The numbers of EPOR^＋ CPCs and EPOR^＋ EPCs were reduced remarkably in NPDR corn pared with the control group （both P（0.01）, whereas rebounded in PDR and PDR-DN groups in varying degrees. Similar changes were observed in respect of the proportion of EPOR^＋ CPCs in CPCs （NPDR vs. control, P（0.01） and that of EPOR^＋ EPCs in EPCs （NPDR vs. control, P〈0.05）. Conclusion Exogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the impaired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR^＋ EPCs associated with ischemia.

Endothelial progenitor cells:Exploring the pleiotropic effects of statins

Statins have become a cornerstone of risk modification for ischaemic heart disease patients. A number of studies have shown that they are effective and safe. However studies have observed an early benefit in terms of a reduction in recurrent infarct and or death after a myocardial infarction,prior to any significant change in lipid profile. Therefore,pleiotropic mechanisms,other than lowering lipid profile alone,must account for this effect. One such proposed pleiotropic mechanism is the ability of statins to augment both number and function of endothelial progenitor cells. The ability to augment repair and maintenance of a functioning endothelium may have profound beneficial effect on vascular repair and potentially a positive impact on clinical outcomes in patients with cardiovascular disease. The following literature review will discuss issues surrounding endothelial progenitor cell(EPC) identification,role in vascular repair,factors affecting EPC numbers,the role of statins in current medical practice and their effects on EPC number.

Sleep-disordered breathing is associated with depletion of circulating endothelial progenitor cells and elevation in pulmonary arterial pressure in patients with decompensated systolic heart failure

Background Sleep-disordered breathing （SDB） is known to occur frequently in and may predict worsening progression of patients with congestive heart failure （CHF）. SDB is also known to play an important role in the development of idiopathic pulmonary arterial hyper- tension （PAH） via inducing endothelial dysfunction and vascular remodeling, a pathological process that can be significantly influenced by factors such as osteoprotegerin （OPG） and endothelial progenitor cells （EPCs）. The objective of this study is to determine if CHF with SDB is associated with changes in OPG, EPCs, and PAIl. Methods EPCs were isolated, cultured, and quantified from CHF patients with SDB （n = 52）, or without SDB （n - 68）. OPG and N-terminal pro-brain natriuretic peptide （NT-proBNP） from each group was analyzed and cor- related with EPCs and the mean pulmonary artery pressure （mPAP） measured by right heart catheterization. Results A significant decrease in circulating EPCs （29.30 ± 9.01 vs. 45.17 ± 10.51 EPCs/x 200 field; P 〈 0.05） was found in CHF patients with SDB compared to those without SDB. Both OPG （789.83 ±89.38 vs. 551.29 ± 42.12 pg/mL; P 〈 0.05） and NT-proBNP （5946.50 ± 1434.50 vs. 3028.60 ± 811.90 ng/mL; P 〈 0.05） were also significantly elevated in SDB CHF patients who also had significantly elevated mPAP （50.2 ± 9.5 vs. 36.4 ± 4.1 mm Hg; P 〈 0.05）. EPC numbers correlated inversely with the episodes of apnea and hypopnea per hour （RDI, r = -0.45, P = 0.037） and blood level of OPG （r =-0.53, P = 0.011）. Although NT-proBNP was also increased significantly in patients with SDB, it had no correlation with either EPCs or RD1. Conclusions SDBdue to hypoxemia from decompensated CHF is associated with （1） OPG elevation, （2） EPC depletion, and （3） mPAP elevation. The inverse relationship of circulating OPG with EPCs suggests a likely mechanism for hypoxemia and OPG in the development of pulmonary vascular dysfunction via depleting EPCs, thus worsening prognosis of CHF.

Effects of Exogenous Sonic Hedgehog Peptide on Proliferation, Adhesion, Migration of Endothelial Progenitor Cells from Peripheral Blood

Summary： In order to study the effects of exogenous sonic hedgehog （shh） peptide on proliferation, adhesion, migration of endothelial progenitor cells （EPCs） from rat peripheral blood, the mononuclear cells were collected from rat peripheral blood by Ficoll density gradient centrifugation. EPCs were iso- lated with adherence screening method and cultured in M199 culture medium with the supplement of VEGF and bFGF. The immunohistochemical staining was used to identify cell markers such as CD133 and VEGFR-2. EPCs were stimulated with exogenous shh peptide of different final concentrations （0.01, 0.1, 1, 10 μg/mL）. The proliferation, adhesion and migration of EPCs were detected by MTT chromom- etry, adhesion test and transwell system, respectively. The results of this study showed that, after 7 days of culture, cells formed clusters, assuming typical cobbles-tone pattern under microscope. After 2 weeks of culture, cells were arranged in cord-like fashion and sometimes grew like ＂micro-vessels＂. Immuno- histochemical staining showed that the cultured cells were positive for both CD133 and VEGFR-2. The proliferation, adhesion and migration of EPCs could be promoted by endogenous shh peptide at concen- trations from 0.1 μg/mL to 10 μg/mL in a concentration-dependent manner. The findings indicate that exogenous shh peptide can enhance EPCs proliferation, adhesion, and migration, which may have a po- tential value for clinical application.

Correlation between Increased Circulating Endothelial Progenitor Cells and Stage of non-Hodgkin Lymphoma

This study aims to examine the levels of circulating endothelial progenitor cells （cEPCs） in the peripheral blood of patients with non-Hodgkin lymphoma （NHL） and their correlation with the tumor stage. Forty-one patients with biopsy-proven NHL and 16 healthy individuals were recruited. Pe- ripheral blood mononuclear cells （PBMCs） were isolated by density gradient centrifugation, and cEPCs were characterized by triple staining using antibodies against CD133, CD34 and vascular endothelial growth factor receptor-2 （VEGFR-2, CD309） and quantified by flow cytometry. In NHL patients, the number of cEPCs was significantly greater than in control group （P=-0.000）. The cEPCs counts in patients with NHL of stage III-1V were significantly greater than in stage I -II （P=-0.010）. FACS analysis revealed that the number of cEPCs in NHL patients had no correlation with the gender （P=0.401） or the pathological category （P=0.852）. It was suggested that the over-expression of cEPCs in NHL patients may serve as a novel biomarker for disease progression in NHL.

Effect of endothelial progenitor cells derived from human umbilical cord blood on oxygen-induced retinopathy in mice by intravitreal transplantation

AIM： To investigate the effect of endothelial progenitor cells（EPCs） labeled by carboxy fluorescein diacetate succinimidyl ester（CFSE） on murine oxygen-induced retinopathy（OIR） by intravitreal transplantation.METHODS： After isolated from human umbilical cord blood mononuclear cells, EPCs were cultivated and then labeled with CFSE in vitro. C57BL/6J mice were placed to75% hyperoxia chamber from P7 to P12 to establish OIR model. At P12, OIR mice were intravitreally injected with1 μL suspension contained 2×105EPCs（EPCs group） or isometric phosphate buffered saline（PBS group）. The contralateral eye of each mice received no injection（OIR group）. Evans blue angiography and frozen section were examined to track the labeled cells in OIR group at P15 and P19. Using retina paraffin sections and adenosinediphos phatase staining at P12 and P19, the effect of EPCs on OIR mice was evaluated quantitatively and qualitatively. RESULTS： The retinas from EPCs group with less non-perfusion area and fewer peripheral tufts wereobserved at P19, comparing with that from PBS or OIR group. The retinopathy in EPCs group receded earlier with less non-ganglion cells and neovascular nuclei,together with relatively regular distribution. The counts of the neovascular nuclei at P19 were reduced by 44% or45%, compared with those of OIR group or PBS group respectively. Three days after EPCs injection, a large number of EPCs appeared in the vitreous cavity and adhered to the retinal surface. While at one week, the cells gathered between the internal plexiform layer and the inner limiting membrane, and some EPCs appeared in retinal vessels.CONCLUSION： EPCs transplantation can participate in the reparative procedure of the neovascularization in OIR.

Endothelial progenitor cells and coronary artery disease:Current concepts and future research directions

Vascular injury is a frequent pathology in coronary artery disease.To repair the vasculature,scientists have found that endothelial progenitor cells(EPCs)have excellent properties associated with angiogenesis.Over time,research on EPCs has made encouraging progress regardless of pathology or clinical technology.This review focuses on the origins and cell markers of EPCs,and the connection between EPCs and coronary artery disease.In addition,we summarized various studies of EPC-capturing stents and EPC infusion therapy,and aim to learn from past technology to predict the future.