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1.
Characterization of endothelial progenitor cells 总被引:1,自引:0,他引:1
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Recent findings regarding pathways of stem/progenitor cell involvement in adult blood vessel growth (postnatal vasculogenesis) suggest new theories for the pathogenesis of vascular anomalies. The somatic growth of vascular malformations and the mysterious pattern of proliferation and involution in infantile hemangioma can no longer be purely understood through the paradigm of angiogenesis. Molecular signals for postnatal vasculogenesis are being discovered in numerous animal models of cancer and ischemia, yet little research has addressed the importance of vasculogenesis in the growth of vascular anomalies. In this review, we discuss early studies that have investigated stem/progenitor cell involvement in the pathophysiology of infantile hemangioma and other congenital vascular anomalies. 相似文献
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Michele Moschetta Yuji Mishima Ilyas Sahin Salomon Manier Siobhan Glavey Angelo Vacca Aldo M. Roccaro Irene M. Ghobrial 《生物化学与生物物理学报:癌评论》2014
Tumor-associated neovasculature is a critical therapeutic target; however, despite significant progress made in the clinical efficacy of anti-vessel drugs, the effect of these agents remains transient: over time, most patients develop resistance, which inevitably leads to tumor progression. To develop more effective treatments, it is imperative that we better understand the mechanisms involved in tumor vessel formation, how they participate to the tumor progression and metastasis, and the best way to target them. 相似文献
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Asakage M Tsuno NH Kitayama J Kawai K Okaji Y Yazawa K Kaisaki S Osada T Watanabe T Takahashi K Nagawa H 《Cancer immunology, immunotherapy : CII》2006,55(6):708-716
Endothelial progenitor cells (EPCs) have been recently found to exist circulating in peripheral blood of adults, and home
to sites of neovascularization in peripheral tissues. They can also be differentiated from peripheral blood mononuclear cells
(PBMNCs). In tumor tissues, EPCs are found in highly vascularized lesions. Few reports exist in the literature concerning
the characteristics of EPCs, especially related to their surface antigen expressions, except for endothelial markers. Here,
we aimed to investigate the surface expression of differentiation markers, and the functional activities of early-outgrowth
of EPCs (EO-EPCs), especially focusing on their antigen-presenting ability. EO-EPCs were generated from PBMNCs, by culture
in the presence of angiogenic factors. These EO-EPCs had the morphological and functional features of endothelial cells and,
additionally, they shared antigen-presenting ability. They induced the proliferation of allogeneic lymphocytes in a mixed-lymphocyte
reaction, and could generate cytotoxic lymphocytes, with the ability to lyze tumor cells in an antigen-specific manner. The
antigen-presenting ability of EO-EPCs, however, was weaker than that of monocyte-derived dendritic cells, but stronger than
peripheral blood monocytes. Since EO-EPCs play an important role in the development of tumor angiogenesis, targeting EPCs
would be an effective anti-angiogenic strategy. Alternatively, due to their antigen-presenting ability, EO-EPCs can be used
as the effectors of anti-tumor immunotherapy. Since they share endothelial antigens, the activation of a cellular immunity
against angiogenic vessels can be expected. In conclusion, EO-EPCs should be an interesting alternative for the development
of new therapeutic strategies to combat cancer, either as the effectors or as the targets of cancer immunotherapy. 相似文献
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Popescu M Munteanu A Isvoranu G Suciu L Pavel B Marinescu B Zagrean L 《Roumanian archives of microbiology and immunology》2011,70(3):109-113
There is relevant evidence concerning the involvement of endothelial progenitor cells in neovascularization and wound healing. In this study we investigated the effects of sevoflurane, a volatile anesthetic with proven cardioprotective virtues, on the mobilization of bone marrow mononuclear cells with endothelial progenitor markers (CD 34+, flk-1 +), an event that may account for the protective effects of delayed anesthetic preconditioning. Male Wistar rats were treated with a mixture of air and sevoflurane (1 MAC) in cycles of 5 minutes, alternating with 5-minutes wash-out periods (the preconditioned group), or ventilated for 30 minutes with room air (control group). Following flow cytometry and immunofluorescence measurements, a considerable increase in circulating CD34+, flk-1 + and CD34+/flk-1 + cells was observed in the preconditioned group beginning at 12 hours after treatment, with a peak value at 24 hours after sevoflurane administration. These cells are a potential source of myocardial regeneration in the context of perioperative or periprocedural ischemia in patients with coronary artery disease. 相似文献
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Endothelial progenitor cells (EPCs), which were first identified in adult peripheral blood mononuclear cells (MNCs), play an important role in postnatal neovascularization. Tissue ischemia augments mobilization of EPCs from bone marrow into the circulation and enhances incorporation of EPCs at sites of neovascularization. Two methods to obtain EPCs from bone marrow, peripheral blood or cord blood MNCs have been evaluated for therapeutic neovascularization: (1) fresh isolation using anti-CD34, anti-KDR or anti-AC133 antibody, and (2) ex vivo expansion of total MNCs. In an immunodeficient mouse model of hindlimb ischemia, systemic transplantation of human ex vivo expanded EPCs improves limb survival through the enhancement of blood flow in the ischemic tissue. A similar strategy also leads to histological and functional preservation of ischemic myocardium of nude rats. Recently, a preclinical study of catheter-based, intramyocardial transplantation ofautologous EPCs in a swine model of chronic myocardial ischemia demonstrated the therapeutic potential of cell-based therapy, with attenuation of myocardial ischemia and improvement in left ventricular function. These favorable outcomes strongly suggest a therapeutic impact of EPC transplantation in clinical settings. Further basic research, with improved understanding of the mechanisms governing homing and incorporation of EPCs, will be still necessary to optimize the methodology of the cell therapy. 相似文献
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Lavergne M Derkaoui M Delmau C Letourneur D Uzan G Le Visage C 《Macromolecular bioscience》2012,12(7):901-910
Human ECFCs contribute to vascular repair. For this reason, they are considered as valuable cell therapy products in ischemic diseases. Porous scaffolds are prepared that are composed of natural polysaccharides, pullulan and dextran, by chemical crosslinking without use of organic solvents. These porous scaffolds, which have pores with an average size of 42 μm and a porosity of 21%, preserve the viability and the proliferation of cord-blood ECFCs. After 7 d of culture in porous scaffolds, ECFCs express endothelial markers (CD31 and vWf) and maintain endothelial functions. The cultured cells can be easily retrieved by enzymatic degradation of the porous scaffolds. In vitro results suggest that the porous scaffold could allow cell delivery of ECFCs for treatment of vascular diseases. 相似文献
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Liu Q Xi Y Terry T So SP Mohite A Zhang J Wu G Liu X Cheng J Ruan KH Willerson JT Dixon RA 《Journal of cellular physiology》2012,227(7):2907-2916
Prostacyclin (PGI2) is a potent vasodilator and important mediator of vascular homeostasis; however, its clinical use is limited because of its short (<2‐min) half‐life. Thus, we hypothesize that the use of engineered endothelial progenitor cells (EPCs) that constitutively secrete high levels of PGI2 may overcome this limitation of PGI2 therapy. A cDNA encoding COX‐1‐10aa‐PGIS, which links human cyclooxygenase‐1 (COX‐1) to prostacyclin synthase (PGIS), was delivered via nucleofection into outgrowth EPCs derived from rat bone marrow mononuclear cells. PGI2‐secreting strains (PGI2‐EPCs) were established by continuous subculturing of transfected cells under G418 selection. Genomic PCR, RT‐PCR, and Western blot analyses confirmed the overexpression of COX‐1‐10aa‐PGIS in PGI2‐EPCs. PGI2‐EPCs secreted significantly higher levels of PGI2 in vitro than native EPCs (P < 0.05) and showed higher intrinsic angiogenic capability; conditioned medium (CM) from PGI2‐EPCs promoted better tube formation than CM from native EPCs (P < 0.05). Cell‐ and paracrine‐mediated in vitro angiogenesis was attenuated when COX‐1‐10aa‐PGIS protein expression was knocked down. Whole‐cell patch‐clamp studies showed that 4‐aminopyridine‐sensitive K+ current density was increased significantly in rat smooth muscle cells (rSMCs) cocultured under hypoxia with PGI2‐EPCs (7.50 ± 1.59 pA/pF; P < 0.05) compared with rSMCs cocultured with native EPCs (3.99 ± 1.26 pA/pF). In conclusion, we successfully created EPC strains that overexpress an active novel enzyme resulting in consistent secretion of PGI2. PGI2‐EPCs showed enhanced intrinsic proangiogenic properties and provided favorable paracrine‐mediated cellular protections, including promoting in vitro angiogenesis of native EPCs and hyperpolarization of SMCs under hypoxia. J. Cell. Physiol. 227: 2907–2916, 2012. © 2011 Wiley Periodicals, Inc. 相似文献
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Di Marco GS Rustemeyer P Brand M Koch R Kentrup D Grabner A Greve B Wittkowski W Pavenstädt H Hausberg M Reuter S Lang D 《PloS one》2011,6(9):e24046
Background
Kidney transplantation (RTx) leads to amelioration of endothelial function in patients with advanced renal failure. Endothelial progenitor cells (EPCs) may play a key role in this repair process. The aim of this study was to determine the impact of RTx and immunosuppressive therapy on the number of circulating EPCs.Methods
We analyzed 52 RTx patients (58±13 years; 33 males, mean ± SD) and 16 age- and gender-matched subjects with normal kidney function (57±17; 10 males). RTx patients received a calcineurin inhibitor (CNI)-based (65%) or a CNI-free therapy (35%) and steroids. EPC number was determined by double positive staining for CD133/VEGFR2 and CD34/VEGFR2 by flow cytometry. Stromal cell-derived factor 1 alpha (SDF-1) levels were assessed by ELISA. Experimentally, to dissociate the impact of RTx from the impact of immunosuppressants, we used the 5/6 nephrectomy model. The animals were treated with a CNI-based or a CNI-free therapy, and EPCs (Sca+cKit+) and CD26+ cells were determined by flow cytometry.Results
Compared to controls, circulating number of CD34+/VEGFR2+ and CD133+/VEGFR2+ EPCs increased in RTx patients. There were no correlations between EPC levels and statin, erythropoietin or use of renin angiotensin system blockers in our study. Indeed, multivariate analysis showed that SDF-1 – a cytokine responsible for EPC mobilization – is independently associated with the EPC number. 5/6 rats presented decreased EPC counts in comparison to control animals. Immunosuppressive therapy was able to restore normal EPC values in 5/6 rats. These effects on EPC number were associated with reduced number of CD26+ cells, which might be related to consequent accumulation of SDF-1.Conclusions
We conclude that kidney transplantation and its associated use of immunosuppressive drugs increases the number of circulating EPCs via the manipulation of the CD26/SDF-1 axis. Increased EPC count may be associated to endothelial repair and function in these patients. 相似文献11.
Petoumenos V Nickenig G Werner N 《Journal of cellular and molecular medicine》2009,13(11-12):4623-4635
Endothelial progenitor cells (EPC) enhance endothelial cell repair, improve endothelial dysfunction and are a predictor for cardiovascular mortality. High-density lipoprotein (HDL) cholesterol levels inversely correlate with cardiovascular events and have vasculoprotective effects. Here we postulate that HDL influences EPC biology. HDL and EPC were isolated according to standard procedures. Differentiation of mononuclear cells into DiLDL/lectin positive cells was enhanced after HDL treatment compared to vehicle. HDL was able to inhibit apoptosis (TUNEL assay, annexin V staining) while proliferation (BrdU incorporation) of early outgrowth colonies after extended cell cultivation (14 days) was increased. Flow chamber experiments revealed an improved adhesion of HDL pre-incubated EPC on human coronary artery endothelial cells (HCAEC) compared to vehicle while HDL treatment of HCAEC prevented adhesion of inflammatory cells. Flow cytometry demonstrated an up-regulation of beta2- and alpha4-integrins on HDL pre-incubated EPC. Blocking experiments revealed a unique role of beta2-integrin in EPC adhesion. Treatment of wild-type mice with recombinant HDL after endothelial denudation resulted in enhanced re-endothelialization compared to vehicle. Finally, in patients with coronary artery disease a correlation between circulating EPC and HDL concentrations was demonstrated. We provide evidence that HDL mediates important vasculoprotective action via the improvement of function of circulating EPC. 相似文献
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The involvement of endothelial progenitor cells in tumor angiogenesis 总被引:11,自引:0,他引:11
Ribatti D 《Journal of cellular and molecular medicine》2004,8(3):294-300
Endothelial progenitor cells (EPCs) have been isolated from peripheral blood CD34, VEGFR-2, or AC 133 (CD133) antigen-positive cells, which may home to site of neovascularization and differentiate into endothelial cells in situ. Endothelial cells contribute to tumor angiogenesis, and can originate from sprouting or co-option of neighbouring pre-existing vessels. Emerging evidence indicate that bone marrow-derived circulating EPCs can contribute to tumor angiogenesis and growth of certain tumors. This review article will summarize the literature data concerning this new role played by EPCs in tumor angiogenesis. 相似文献
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EPCs (endothelial progenitor cells) regenerate the vascular endothelial cells and keep the integrity of the vascular endothelium and thus may retard the onset of atherosclerosis. Steady state levels of EPCs in the circulation were found to be correlated with cardiovascular event risks. Given the close relationship between insulin and the cardiovascular system, we tested the long-term effects of moderate-dose insulin treatment on bone marrow-derived EPCs. Rat bone marrow EPCs were exposed to various levels of insulin under normal (5 mmol/l) or high (40 mmol/l) glucose conditions for 7 days. Insulin at levels near the physiological range (0.1, 1 nmol/l) up-regulated EPCs proliferation, stimulated NO (nitric oxide) production and reduced EPC senescence and ROS (reactive oxygen species) generation under both normal- and high-glucose conditions. Glucose exerted deleterious effects on EPCs contrary to insulin. Western blot analysis suggested concomitant decrease of Akt phosphorylation and eNOS (endothelial nitric oxide synthase) expression by high-glucose treatment and increase with insulin administration. Thus, insulin promoted several activities of EPCs, which suggested a potential endothelial protective role of insulin. Akt/eNOS pathway may be involved in the modulation of EPCs function by glucose and insulin. 相似文献
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Zisch AH 《Current opinion in biotechnology》2004,15(5):424-429
Adult bone marrow and peripheral blood contain small subsets of mononuclear cells that can be differentiated into endothelial-like cells in vitro. Experimental and clinical transplantation of such cell isolates--often referred to as endothelial stem/progenitor cells--into ischaemic or infarcted areas shows their incorporation into sites of new vessel growth along with improvement of regional blood flow. Emerging evidence suggests that these beneficial effects on vascular growth can be attributed to the paracrine activation of resident endothelial cells, rather than their integration into new endothelium. Autologous endothelial progenitor cells can also substitute for native vessel-derived endothelial cells in tissue-engineered vascular autografts. 相似文献
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Endothelial progenitor cells (EPCs) are known to promote neovascularization in ischemic diseases. Recent evidence from our
group suggested that CREB-binding protein (CBP) plays an important role in thrombin-induced EPCs migration. However, whether
CBP could regulate EPCs angiogenic properties is unknown. In the present study, we investigated whether CBP silencing could
inhibit thrombin-induced EPCs angiogenesis. EPCs isolated from the bone marrow of Sprague–Dawley rats were cultured and identified,
and then were treated by thrombin alone or combined with CBP-shRNA lentivirus. The effect of CBP silencing on EPCs proliferation
was assessed using BrdU incorporation assay. Cell adhesion and tube formation were detected to evaluate the angiogenic functions.
Finally, mRNA and protein expression of relevant angiogenic genes were examined by real-time PCR, western-blot, and enzyme-linked
immunoassay respectively. Luciferase reporter gene assay was performed to evaluate NF-κB activity. Administration of thrombin
significantly promoted EPCs proliferation and adhesion. Thrombin also increased the tube formation in Matrigel assay. However,
these effects of thrombin were abolished by CBP gene silencing. CBP silencing also abrogated thrombin-induced increases of
integrin β2 expression. In thrombin-induced EPCs, CBP silencing significantly decreased the secretion of VEGF, IL-6 and suppressed
NF-κB activity. In conclusion, thrombin-induced EPCs proliferation, adhesion, and tube formation were inhibited by CBP silencing,
indicating that CBP plays an important role in thrombin-induced EPCs neovascularization. 相似文献
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Kaiser R Friedrich D Chavakis E Böhm M Friedrich EB 《Journal of cellular and molecular medicine》2012,16(10):2387-2393
Homing of endothelial progenitor cells (EPCs) is crucial for neoangiogenesis, which might be negatively affected by hypoxia. We investigated the influence of hypoxia on fibronectin binding integrins for migration and cell‐matrix‐adhesion. AMP‐activated kinase (AMPK) and integrin‐linked kinase (ILK) were examined as possible effectors of hypoxia.Human EPCs were expanded on fibronectin (FN) and integrin expression was profiled by flow cytometry. Cell‐matrix‐adhesion‐ and migration‐assays on FN were performed to examine the influence of hypoxia and AMPK‐activation. Regulation of AMPK and ILK was shown by Western blot analysis. We demonstrate the presence of integrin β1, β2 and α5 on EPCs. Adhesion to FN is reduced by blocking β1 and α5 (49% and 2% of control, P < 0.05) whereas α4‐blockade has no effect. Corresponding effects were shown for migration. Hypoxia and AMPK‐activation decrease adhesion on FN. Although total AMPK‐expression remains unchanged, phospho‐AMPK increases eightfold.The EPCs require α5 for adhesion on FN. Hypoxia and AMPK‐activation decrease adhesion. As α5 is the major adhesive factor for EPCs on FN, this suggests a link between AMPK and α5‐integrins. We found novel evidence for a connection between hypoxia, AMPK‐activity and integrin activity. This might affect the fate of EPCs in ischaemic tissue. 相似文献
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Ghaly T Rabadi MM Weber M Rabadi SM Bank M Grom JM Fallon JT Goligorsky MS Ratliff BB 《American journal of physiology. Renal physiology》2011,301(4):F802-F812
Sepsis and its complications are associated with poor clinical outcomes. The circulatory system is a well-known target of lipopolysaccharide (LPS). Recently, several clinical studies documented mobilization of endothelial progenitor cells (EPCs) during endotoxemia, with the probability of patients' survival correlating with the rise in circulating EPCs. This fact combined with endotoxemia-induced vascular injury led us to hypothesize that the developing functional EPC incompetence could impede vascular repair and that adoptive transfer of EPCs could improve hemodynamics in endotoxemia. We used LPS injection to model endotoxemia. EPCs isolated from endotoxemic mice exhibited impaired clonogenic potential and LPS exerted Toll-like receptor 4-mediated cytotoxic effects toward EPCs, which was mitigated by embedding them in hyaluronic acid (HA) hydrogels. Therefore, intact EPCs were either delivered intravenously or embedded within pronectin-coated HA hydrogels. Adoptive transfer of EPCs in LPS-injected mice improved control of blood pressure and reduced hepatocellular and renal dysfunction. Specifically, EPC treatment was associated with the restoration of renal microcirculation and improved renal function. EPC therapy was most efficient when cells were delivered embedded in HA hydrogel. These findings establish major therapeutic benefits of adoptive transfer of EPCs, especially when embedded in HA hydrogels, in mice with LPS-induced endotoxemia, and they argue that hemodynamic and renal abnormalities of endotoxemia are in significant part due to developing incompetence of endogenous EPCs. 相似文献