Circulating Endothelial Progenitor Cells Research Articles

Role of circulating endothelial progenitor cells in patients with breast cancer

Objective The aim was to assess the role of the circulating endothelial progenitor cells (CEPCs) in stages of breast cancer (BC) in patients. Materials and Methods We reviewed papers on the relation between CEPCs and stages of BC from Medline databases (PubMed, Medscape, Science Direct, and EMF-Portal) and all materials available on the internet from 1994 to 2016. The initial search presented 100 articles, of which, 30 met the inclusion criteria. The articles studied the relation between endothelial progenitor cells and stages of BC. If the studies did not fulfill the inclusion criteria, they were excluded. Study quality assessment included whether ethical approval was gained, eligibility criteria specified, appropriate controls, adequate information, and defined assessment measures. Comparisons were made by structured review with the results tabulated. Findings Endothelial progenitor cells counts were significantly higher in advanced stages of BC compared with those with early stages and controls in almost all the studied publications. Conclusion Our review concludes CEPCs elevation in the blood of patients is a useful marker of tumor angiogenesis and progression and early predictor of metastasis in patients with BC.

The endothelial status reflected by circulating endothelial cells, circulating endothelial progenitor cells and soluble thrombomodulin in patients with mild and resistant hypertension

BackgroundThe aim of the present study was to evaluate endothelial status by measuring the concentration of novel markers of endothelial dysfunction (ED): a number of circulating endothelial cells (CECs), circulating endothelial progenitor cells (CEPCs) and their ratio (CEPCs/CECs) as well as a traditional parameter - soluble thrombomodulin (sTM) in patients with resistant (RH) and mild hypertension (MH). Materials and methodsThirty patients with MH and thirty subjects with RH were involved in the study. The control group included thirty-three age and sex-matched normotensive volunteers. We used multicolor flow cytometry for CECs and CEPCs analysis and the commercial human sTM ELISA kit to measure plasma sTM concentration. ResultsAn elevated CECs number and a decreased CEPCs/CECs ratio was found in MH as well as in RH patients in comparison with normotensive volunteers. CECs correlated positively with an increased triglycerides in MH patients and an elevated LDL-cholesterol and hsCRP in RH group. Positive correlation between CEPCs and LDL-cholesterol level was observed in both types of hypertension. ConclusionsThe results of the present study suggest that an endothelial alteration accompanies hypertension. The number of CECs reflecting the extent of endothelial damage does not appear to be related to the severity of disease. The drastically decreased ratio between CEPCs and CECs observed in both groups of patients suggests an inadequate process of endothelial regeneration. Among analyzed factors inflammation and lipid abnormalities may have significant contribution in endothelial pathology in hypertension.

GW29-e0550 Isolation, Culture and Identification of Circulation Endothelial Progenitor cells in Peripheral Blood

GW29-e0550 Isolation, Culture and Identification of Circulation Endothelial Progenitor cells in Peripheral Blood

No Differences in Levels of Circulating Progenitor Endothelial Cells or Circulating Endothelial Cells Among Patients Treated With Ticagrelor Compared With Clopidogrel During Non- ST -Segment-Elevation Myocardial Infarction.

BackgroundTicagrelor use during acute coronary syndromes demonstrated a decrease in all‐cause mortality in the PLATO (Platelet Inhibition and Patient Outcomes) trial. This effect has been attributed to a non–platelet‐derived improvement in endothelial function. The aim of this study was to determine differences in the number of endothelial progenitor cells and/or circulating endothelial cells found in peripheral blood in patients treated with either ticagrelor or clopidogrel during non–ST‐segment–elevation myocardial infarction.Methods and ResultsIn this multicenter, randomized study (NCT02244710), patients were considered for inclusion after non–ST‐segment–elevation myocardial infarction whenever they were P2Y12‐inhibitor naïve. Ticagrelor and clopidogrel were allocated at a 1:1 ratio. Blood samples for determining endothelial progenitor cells and circulating endothelial cells were extracted before the antiplatelet loading dose, 48 hours after presentation of index symptoms, and 1 month after the event. A multichannel cytometer was used for optimal cell characterization. A total of 96 patients fulfilled the inclusion criteria. Circulating endothelial cell levels corrected by white blood cells were as follows at baseline, 48 hours, and 1 month: 44 (28–64), 50 (33–63), and 38 (23–62) cells/mL, respectively, for clopidogrel and 38 (29–60), 45 (32–85), and 35 (24–71) cells/mL, respectively, for ticagrelor (P=0.6). Endothelial progenitor cell levels were 29 (15–47), 27 (15–33), and 18 (10–25) cells/mL, respectively, for clopidogrel and 20 (11–33), 22 (12–32), and 18 (11–29) cells/mL, respectively, for ticagrelor (P=0.9). No differences in intraindividual changes were found.ConclusionsPatients treated with ticagrelor during non–ST‐segment–elevation myocardial infarction, in comparison to clopidogrel, showed similar levels of endothelial progenitor cells and circulating endothelial cells. These data suggest that the endothelial protective effect mediated by ticagrelor is not related to bone marrow physiology modulation.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT02244710.

Hyperbilirubinemia-induced pro-angiogenic activity of infantile endothelial progenitor cells

ObjectivesBilirubin, a by-product of heme degradation, is suggested to have a role for vascular protection. There is increasing evidence that bilirubin may directly affect the function and secretory activity of endothelial cells. In this study, potential effect of hyperbilirubinemia on biological features of circulation endothelial progenitor cells (cEPCs) isolated from infants was investigated. MethodsCirculation concentration, differentiation and migratory activity of cEPCs isolated from infants with (n = 111) or without (n = 73) hyperbilirubinemia were analyzed. Then, the potential beneficial effect of conditioned medium of cEPCs from infants with or without hyperbilirubinemia was examined on experimental mouse wounds. ResultsOur results revealed significantly higher percentages of cEPCs in infants with hyperbilirubinemia. Cell proliferation, and migratory properties of cEPCs isolated and expanded from infants with hyperbilirubinemia were significantly improved. Also, the conditioned medium of cEPCs from hyperbilirubinemic infants possessed a superior beneficial effect on wound healing, which was associated with increased protein levels of VEGF, IL-10, and Pho-ERK/ERK, and decreased TNF-α in the wound tissues. ConclusionsOur results showed that hyperbilirubinemia can activate migration, proliferating and angiogenic properties of cEPCs. Hyperbilirubinemia can promote the proangiogenic secretory activity of cEPCs, thereby resulting in enhancement of their regenerative wound healing properties.

Identification of MicroRNA-124 as a Major Regulator of Enhanced Endothelial Cell Glycolysis in Pulmonary Arterial Hypertension via PTBP1 (Polypyrimidine Tract Binding Protein) and Pyruvate Kinase M2.

Pulmonary arterial hypertension (PAH) is characterized by abnormal growth and enhanced glycolysis of pulmonary artery endothelial cells. However, the mechanisms underlying alterations in energy production have not been identified. Here, we examined the miRNA and proteomic profiles of blood outgrowth endothelial cells (BOECs) from patients with heritable PAH caused by mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene and patients with idiopathic PAH to determine mechanisms underlying abnormal endothelial glycolysis. We hypothesized that in BOECs from patients with PAH, the downregulation of microRNA-124 (miR-124), determined with a tiered systems biology approach, is responsible for increased expression of the splicing factor PTBP1 (polypyrimidine tract binding protein), resulting in alternative splicing of pyruvate kinase muscle isoforms 1 and 2 (PKM1 and 2) and consequently increased PKM2 expression. We questioned whether this alternative regulation plays a critical role in the hyperglycolytic phenotype of PAH endothelial cells. Heritable PAH and idiopathic PAH BOECs recapitulated the metabolic abnormalities observed in pulmonary artery endothelial cells from patients with idiopathic PAH, confirming a switch from oxidative phosphorylation to aerobic glycolysis. Overexpression of miR-124 or siRNA silencing of PTPB1 restored normal proliferation and glycolysis in heritable PAH BOECs, corrected the dysregulation of glycolytic genes and lactate production, and partially restored mitochondrial respiration. BMPR2 knockdown in control BOECs reduced the expression of miR-124, increased PTPB1, and enhanced glycolysis. Moreover, we observed reduced miR-124, increased PTPB1 and PKM2 expression, and significant dysregulation of glycolytic genes in the rat SUGEN-hypoxia model of severe PAH, characterized by reduced BMPR2 expression and endothelial hyperproliferation, supporting the relevance of this mechanism in vivo. Pulmonary vascular and circulating progenitor endothelial cells isolated from patients with PAH demonstrate downregulation of miR-124, leading to the metabolic and proliferative abnormalities in PAH ECs via PTPB1 and PKM1/PKM2. Therefore, the manipulation of this miRNA or its targets could represent a novel therapeutic approach for the treatment of PAH.

Enhanced Integrin α4β1-Mediated Adhesion Contributes to a Mobilization Defect of Endothelial Progenitor Cells in Diabetes.

Diabetes is associated with a deficit of circulating endothelial progenitor cells (EPCs), which has been attributed to their defective mobilization from the bone marrow. The basis for this mobilization defect is not completely understood, and we sought to determine if hyperglycemic conditions enhanced EPC adhesion. We found that culturing EPCs in high glucose media increased adhesion to bone marrow stromal cells. This enhanced adhesion was associated with decreased expression of protein kinase A regulatory subunit 1β (PRKAR1β), activation of protein kinase A (PKA), and phosphorylation of α4-integrin on serine 988. This potentiated adhesion was reversed by treatment with a PKA inhibitor, overexpression of PRKAR1β, or expression of a phosphorylation-defective α4-integrin variant (α4[S988A]). Using a model of type 1 diabetes, we showed that α4(S988A)-expressing mice have more circulating EPCs than their wild-type counterparts. Moreover, diabetic α4(S988A) mice demonstrate enhanced revascularization after hind limb ischemia. Thus, we have identified a novel signaling mechanism activating PKA in diabetes (downregulation of an inhibitory regulatory subunit) that leads to deficits of circulating EPCs and impaired vascular repair, which could be reversed by α4-integrin mutation.

Circulation Enrichment of Functional Endothelial Progenitor Cells by Infantile Phototherapy.

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.

Abstract 355: Progenitor Cells and Extracellular Vesicles as Biomarkers for Vasculitis

Background: Patients with vasculitis (VS) have complex organ- and life-threatening disease manifestations due to autoimmune-mediated inflammatory vascular damage and an increased risk of cardiovascular disease (CVD). Accurate biomarkers do not exist for VS. Cells release extracellular vesicles (EVs) in the setting of activation, injury, or death. In patients with diabetes mellitus and CVD, the effects of the inflammatory cascade, platelets and endothelium, positively correlate with levels of EVs bearing receptors for CD3, CD41, or CD105, and negatively correlate with levels of circulating endothelial progenitor cells (CPCs). Because VS is characterized by systemic inflammation, platelet activation and endothelial damage, this group of diseases may have unique effects on EVs and CPCs. This study evaluated a high dimensional flow cytometry approach to profiling EVs and CPCs in plasma to discern a biomarker pattern in VS. Methods: Levels of CPCs and EVs were measured with a panel of cell surface markers in 10 VS patients and 5 age-similar healthy controls (HC). Data were acquired on a modified Becton Dickinson FACSCanto. Results: Although no significant increase in CPCs in VS compared with HC was detected, the standard deviation of CPC levels in VS was more than double that in HC (SD=574 vs. 165, p=0.081), suggesting heterogeneity in the VS group. EV subsets with lower concentrations in VS, compared with HC, included: Annexin + CD3 + double-positive T Lymphocyte (p=0.026) and CD105 + CD64 + double-positive activated Macrophage (p=0.030). CD144 + CD105 + double-positive endothelial EVs were only detected in a subset of VS and not in HC. CD31 + CD41a + double-positive platelet EVs were increased in VS compared with HC (894 (580) vs. 416 (128), p=0.004). Conclusion: This proof of concept study discovered a distinct EV pattern that correlates with a diagnosis of VS, suggesting that cell- and vesicle-based assays could be useful biomarkers in evaluating VS. This pattern is different from that found in patients with diabetes mellitus and CVD. Larger studies could seek to elucidate correlations between CPCs and disease activity and identify a unique EV signature for VS with increased risk for CVD.

Abstract P3-07-61: Predictors of response and follow up biomarkers for metronomic chemotherapy with cyclophosphamide and celecoxib in advanced breast cancer patients

Abstract Low-dose metronomic chemotherapy (MC) with Cyclophosphamide (Cy) and Celecoxib (Cel) has demonstrated to be effective and well-tolerated in advanced breast cancer patients (ABCP) but predictive markers of response or follow-up are lacking. Given the antiangiogenic properties of MC we analyzed several angiogenesis-related biomarkers and evaluated their potential role as predictors of response or treatment follow-up of ABCP treated with MC. Treatment plan: Patients received Cy 50 mg p.o./day + Cel 200 mg p.o./ bid. Cellular parameters: Circulating endothelial cells (CEC) and Circulating progenitor endothelial Cells (CEP) were determined by Flow Cytometry. Serologic parameters: Serum levels of vascular endothelial growth factor (VEGF), VEGF-C, soluble VEGF Receptors 2 and 3 (sVEGFR-2, sVEGFR-3) and Thrombospondin-1 (TSP-1) were determined by ELISA. Blood samples were collected before and during treatment. Twenty patients were enrolled. Response Rate was 5% and Clinical Benefit (CB) 55%. Most of the patients showed prolonged stable disease (SD≥24 weeks). Biomarkers were determined in all patients. Levels of CEC and CEP showed no clear trend variations during treatment. However, levels of CEC significantly increased at the time of disease progression in those patients who showed CB (P=0.014). Also baseline values of CEC and CEP showed marginally significant associations withTime To Progression. Serum VEGF concentration decreased during treatment (P=0.050) while sVEGFR-2 increased (P=0.005). VEGF-C, sVEGFR-3 and TSP-1 showed non-significant variations. VEGF/sVEGFR-2 ratio decreased during treatment (P=0.041), whereas VEGF/TSP-1, and VEGF-C/sVEGFR-2 ratios showed non-significant variations. Baseline values of VEGF, and VEGF/sVEGFR-2 showed negative and significant associations with TTP (P=0.0354 and P=0.0300, respectively) while sVEGFR-2 did not. When considering the two variables together, the goodness of prediction was not improved. To confirm the value of baseline VEGF and VEGF/sVEGFR-2 as predictors of response, we used the 50th percentile as a cutoff value to analyze the % of progression free survival. Patients with values lower than the 50th percentile for both biomarkers showed longer TTP (P=0.0001 and P=0.0008, respectively). The treatment had anti-angiogenic effect (VEGF decrease and sVEGFR-2 increase). The absence of variation in VEGF-C and sVEGFR-3 would indicate the lack of effect on lymphangiogenesis. Increased levels of CEC could be useful for detecting progression. If confirmed with a higher number of patients, baseline VEGF and VEGF/sVEGFR-2 values could be useful as early predictors of response. Citation Format: Perroud HA, Alasino CM, Rico MJ, Menacho-Marquez MA, Mainetti LE, Queralt F, Pezzotto SM, Rozados VR, Scharovsky G. Predictors of response and follow up biomarkers for metronomic chemotherapy with cyclophosphamide and celecoxib in advanced breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-61.

Revisiting tumor angiogenesis: vessel co-option, vessel remodeling, and cancer cell-derived vasculature formation.

Tumor growth and metastasis depend on the establishment of tumor vasculature to provide oxygen, nutrients, and other essential factors. The well-known vascular endothelial growth factor (VEGF) signaling is crucial for sprouting angiogenesis as well as recruitment of circulating progenitor endothelial cells to tumor vasculature, which has become therapeutic targets in clinical practice. However, the survival benefits gained from targeting VEGF signaling have been very limited, with the inevitable development of treatment resistance. In this article, we discuss the most recent findings and understanding on how solid tumors evade VEGF-targeted therapy, with a special focus on vessel co-option, vessel remodeling, and tumor cell-derived vasculature establishment. Vessel co-option may occur in tumors independently of sprouting angiogenesis, and sprouting angiogenesis is not always required for tumor growth. The differences between vessel-like structure and tubule-like structure formed by tumor cells are also introduced. The exploration of the underlying mechanisms of these alternative angiogenic approaches would not only widen our knowledge of tumor angiogenesis but also provide novel therapeutic targets for better controlling cancer growth and metastasis.

Circulating Endothelial Progenitor Cells and Their Relation to Thrombosis in Paroxysmal Nocturnal Hemoglobinuria

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder. Chronic intravascular hemolytic anemia, bone marrow failure and thrombophilia are the main clinical findings. Thrombosis is one of the most important cause of morbidity and mortality of this disease. Multiple factors are held responsible for thrombotic tendency in these patients. Endothelial progenitor cells (EPCs) originate from primitive hematopoietic stem cells and are able to turn into endothelial cells. There are extremely small numbers of EPCs in the circulation under normal conditions. The level of EPCs is considered to be indicative of restoration capacity in case of vascular disease and potential damage. Lower EPC levels are also considered as a risk factor in cardiovascular diseases. In this study, our aim was to investigate circulating EPCs in PNH and their relationship with thrombosis. Seventeen patients with PNH, 18 patients with aplastic anemia and 10 healthy volunteers were included in the study. CD309, CD133 and CD34 antibodies were used in order to determine circulating EPCs by flow cytometry and cells which expressed all three antibodies were analyzed as EPC. Prepared samples were read using a prepared list mode software for endothelial progenitor cells on FACS Diva software in BD FACS Canto II device with 6 color lasers and a total of 1,000,000 cells per analysis were evaluated. EPC levels were compared between untreated PNH patients and who were on eculizumab therapy. Statistical analysis was performed using SPSS 22.0 software. The distribution of variables was evaluated by Kolmogorov-Smirnov test, the analysis of quantitative data was evaluated by ANOVA, Kruskal-Wallis, Mann-Whitney U tests and the analysis of the qualitative data was evaluated by chi-square test.Findings and Discussion: The thrombotic complications were observed in five PNH patients. All of these patients had a history of portal vein thrombosis. One of them also had a history of peripheral arterial disease and amputation related to this. There was not a significant difference in EPC levels between patients with and without a history of thrombosis (p>0,05). We also did not find any significant difference between levels of EPC's in PNH groups with or without eculizumab therapy (p˃0,05). There was no significant difference in levels of EPC between aplastic anemia and PNH groups (p ˃ 0,05). However, we found a significant positive correlation between the levels of EPC and LDH in multivariate analysis (p < 0,05). This finding suggests that hemolysis causes vascular endothelium and promotes new blood vessel formations. Increased EPCs in PNH might be an indirect indicator for vascular endothelium damage in PNH.TableGeneral Features and Rates of EPC of PNH, AA, Healthy Volunteers GroupsAplastic Anemia groupPNH groupControl grouppAgemean±s.smedian (min-max)40.0±14.7 37.5 (20.0-67.0)41.9±13.9 43.0 (19.0-78.0)29.3±3.5 29.5(24.0-34.0)0.047SexFemale n-% Male n-%7 38,9% 11 61.1%9 52.9% 8 47.1%5 50% 5 50%0.687EPC(%)mean±s.s median (min-max)0.2% 0.2% 0.1% (0.0-0.6%)0.3%±0.3% 0.1% (0.0-0.9%)0.1%±0.0% %0,0(%0,0-0,2)0.393All Events (x1000)mean±s.s median (min-max)617±172* 565 (360-914)588±255* 471 (250-1000)878±143 950(655-1000)0.003CD309 and CD34mean±s.s median (min-max)0.003±0.002 0.002 (0.001-0.007)0.005±0.004 0.000-0.011)0.001±0.001 0.001 (0.000-0.002)0.009CD133mean±s.s median (min-max)45.8±36.3 58.3 (0.0-88.2)45.8±39.6 60 (0.0-94.7)42.0±19.4 46.4 (11.1-81.3)0.867ANOVA / Kruskal-Wallis / Mann-Whitney U test / Chi-square test*The difference with the control group, p <0.05EPCs: Endothelial progenitor cells DisclosuresYenerel:Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Abstract 14043: Enhanced Integrin α4β1-mediated Adhesion Contributes to a Mobilization Defect of Endothelial Progenitor Cells in Diabetes

While previous studies have identified a deficit of circulating endothelial progenitor cells (EPCs) in diabetic conditions (diabetic “mobilopathy”), the basis for these deficits are not completely understood. To model the adhesive properties of EPCs in diabetic conditions, we cultured these cells in high glucose and found that they had stronger adhesion to bone marrow stromal cells. This enhanced adhesion was associated with decreased expression of protein kinase A regulatory subunit 1β (PRKAR1β), consequent activation of protein kinase A (PKA), and phosphorylation of the α4 integrin on serine 988. The potentiating effects of high glucose on adhesion were mimicked by direct PKA activation and reversed by treatment with a PKA inhibitor, overexpression of PRKAR1β or expression of a phosphorylation-defective α4 integrin (α4-S988A). Using the STZ model of type I diabetes, we show that α4-S988A-expressing mice have more circulating EPCs than do their wild type counterparts (2.6 ± 0.5 fold). Furthermore, the diabetic α4-S988A mice demonstrate enhanced revascularization (1.50 ± 0.3 fold vs. WT) and tissue repair after hind limb ischemia. Thus, hyperglycemic conditions potentiate the adhesion of EPCs to bone marrow stromal cells which results in an in vivo mobilization defect. Mutational reversal of this increased adhesion liberates EPCs and promotes re-endothelialization in ischemic tissues, suggesting a potential therapeutic target to treat diabetic vascular complications.

Circulating endothelial cells (CECS) and circulating endothelial progenitor cells (CEPCS) in septic and non-infectious systemic inflammatory response syndrome

Endothelial dysfunction plays a key role in sepsis physiopathology, leading to multiorgan failure and death. Circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPCs) may be elevated in septic syndrome as a result of endothelial damage. Previous studies have shown conflicting results and their role in septic syndrome remains unclear [1, 2].

Meta-Analysis of Circulating Endothelial Cells and Circulating Endothelial Progenitor Cells as Prognostic Factors in Lung Cancer.

The aim of this study was to analyze the prognostic implications of pretreatment circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPCs) for the survival of patients with lung cancer. Relevant literature was identified using Medline and EMBASE. Patient clinical characteristics, overall survival (OS) and progression-free survival (PFS) together with CEC and CEPC positive rates before treatment were extracted. STATA 12.0 was used for our analysis and assessment of publication bias. A total of 13 articles (8 for CEC and 5 for CEPC, n=595 and n=244) were pooled for the global meta-analysis. The odds ratio (OR) for OS predicted by pretreatment CECs was 1.641 [0.967, 2.786], while the OR for PFS was 1.168 [0.649, 2.100]. The OR for OS predicted by pretreatment CEPCs was 12.673 [5.274, 30.450], while the OR for PFS was 4.930 [0.931, 26.096]. Subgroup analyses were conducted according to clinical staging. Odds ratio (OR) showed the high level of pretreatment CECs only correlated with the OS of patients with advanced lung cancer (stage III-IV). High counts of CECs seem to be associated only with worse 1-year OS in patients with lung cancer, while high level of pretreatment CEPCs correlate with both worse PFS and OS.

Effects of electroacupuncture on angiogenesis after ischemia and reperfusion

Objective To explore the effect of eletroacupuncture (EA) on angiogenesis after cerebral ischemia and reperfusion through observing the number of peripheral blood endothelial progenitor cells (EPCs) and the expression of vascular endothelial growth factor (VEGF) in the hippocampus. Methods Among 50 male Sprague-Dawley (SD) rats, 10 were randomly selected as a control group (CG). Qi deficiency and blood stasis were induced in the other 40 rats by intragastric administration of dahuang daily for 7 days. A model of focal cerebral ischemia and reperfusion injury was then created by thread-occlusion of the middle cerebral artery, except in 10 rats selected for the sham operation group (SOG) who received the same operation without tightening the thread. The successfully modeled rats were divided into a model group (MG, n=10) and an electroacupuncture group (EAG, n=10). The rats in EAG started acupuncture treatment the next day after modeling, while no treatment was given to those in the other groups. On day 1, 3 and 7 after the modeling, the neurological functioning of the 4 groups was assessed using Basso-Beattie-Bresnahan locomotion scoring and the number of EPCs in the peripheral circulation was detected by flow cytometry. On the 8th day, all the rats were decapitated and the VEGF expression was detected immunohistochemically. Results The average BBB locomotion score of the EAG rose significantly from (4.50±1.05) on day 1, to (13.67±1.21) on day 3, and then further to (20.00±0.89) by day 7, significantly higher than that of MG at the same time points, but still significantly lower than that of the control group. The average number of EPCs in the peripheral circulation in the MG also increased from (26.83±6.05) on day 1 to (33.67±5.39) on day 3, and decreased to (32.83±5.04) on day 7 after modeling, significantly lower than that of the CG [(45.50±9.40), (42.17±4.62) and (41.33±5.50)], the SOG [(58.00±8.05), (59.67±4.84) and (53.83±5.38)] and the EAG [(66.17±4.36), (127.50±73.75) and (55.00±35.15)] at each time point. After occlusion, the average expression of VEGF-positive cells in the hippocampus of the EAG [(27.80±2.39)%] was significantly higher than that of the MG, and both were significantly higher than that of the CG. Conclusions Eletroacupuncture can up-regulate VEGF expression and EPCs in the peripheral blood in rats after cerebral ischemia-reperfusion, which can promote angiogenesis and neural functional recovery. Key words: Eletroacupuncture; Brain; Ischemia; Endothelial growth factors; Endothelial progenitor cells

Изучение количества циркулирующих прогениторных клеток эндотелия у больных сахарным диабетом 1 типа

Aim. Circulating progenitor endothelial cells (CPCs) play an important role in the regeneration of damaged vascular endothelium. We aimed to study the effect of type 1 diabetes mellitus (DM) on the number of different lines of CPCs.Methods. The number of different lines of CPCs was evaluated by flow cytometry in 45 patients with type 1 DM (mean age: 26,6±6,5 years) of different duration and 14 healthy volunteers.Results. The number of CPCs in the peripheral blood flow of patients with type 1 DM was significanlty reduced compared with that in healthy volunteers and had a reliable inverse correlation with glycated haemoglobin (HbA1c).Conclusions. The number of CPCs in the peripheral blood flow of patients with type 1 DM depended on the level of DM compensation. Of the different lines of CPCs, Lin-CD34+ cells were significantly reduced by 42% (p=0,006), Lin-CD34+c-Kit- cells by 42% (p=0,007) and Lin-CD34+c-Kit+ cells by 41% (p=0,022). Thus, the number of CPCs in the peripheral blood of patients with type 1 DM is reduced with higher levels of HbA1c.

Identification of the origin of circulating endothelial progenitor cells

Identification of the origin of circulating endothelial progenitor cells

Circulating endothelial progenitor cell: a promising biomarker in clinical oncology.

Human cancers are endowed with sustained vascularization capability, and their growth, invasion, and metastasis are vascularization dependent. Recently, accumulated body of evidence suggests that endothelial progenitor cells (EPCs) can support vasculogenesis and induce angiogenesis through paracrine mechanisms. In addition, numerous clinical studies have revealed the increase in the number of EPCs in the peripheral blood of cancer patients and demonstrated the correlation of circulating EPCs (CEPCs) with the clinical outcomes. This review highlights current enrichment procedures and methods for the detection of CEPCs and different biomarkers to identify CEPCs as well as the functions of EPCs in tumor vascularization. Furthermore, we systematically review available studies on the clinical relevance of CEPCs in cancer patients to explore the potential diagnostic and prognostic values of CEPCs. Although several contrasting results exist, CEPCs can conceivably serve as a promising biomarker for the early diagnosis, prognosis prediction, and treatment response indication in the future. Additionally, further well-designed clinical studies with larger sample size and unique, specific enumeration procedures are warranted to achieve further insight into the clinical implications of CEPCs.

The number of circulating endothelial progenitor cells in healthy individuals – Effect of some anthropometric and environmental factors (a pilot study)

PurposeThe aim of the study was the evaluation of the number of circulating endothelial progenitor cells (CEPCs) in healthy people and the assessment of the variability of quantitative of CEPCs after 6 weeks. Material and methodsThe study involved 48 healthy individuals; the group consisted of 24 men and 24 women; the mean age of 34. The criterion for the patients’ eligibility for the study was the absence of diabetes, thrombosis and cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. Neither did the respondents take any medication that could clearly affect the value of the results. In the whole blood samples the number of circulating endothelial progenitor cells was determined using flow cytometry. During the analysis the fluorescence of 100,000 cells was measured. CEPCs were identified with immunophenotype CD45−, CD31+, CD34+, CD133+. ResultsIn the study, the median of the number of circulating endothelial progenitor cells in the whole group was 0.41/μL. There was also recorded an increased number of CEPCs after 6 weeks, as compared to the baseline; the difference was significant. There were no differences in the number of CEPCs between the women and the men. There was found no effect on the number of CEPCs factors such as: smoking, physical activity and alcohol consumption. ConclusionsThe study showed that in healthy individuals the gender had no essential effect on the number of endothelial progenitor cells. Based on the demographic and lifestyle data acquired, it is difficult to explain the increase number of CEPCs after 6 weeks.