Chabut D, Fischer Anne-Marie, Helley D, Colliec-Jouault Sylvia (2004). Low molecular weight fucoidan promotes FGF-2-induced vascular tube formation by human endothelial cells, with decreased PAI-1 release and ICAM-1 downregulation. Thrombosis Research, 113(1), 93-95. Publishers official version : https://doi.org/10.1016/j.thromres.2004.01.013 , Open Access version : https://archimer.ifremer.fr/doc/00000/2115/. ...

Blood vessel networks expand inside a 2-step process that begins with vessel sprouting and is followed by vessel anastomosis. in zebrafish we now display that macrophages promote tip cell fusion downstream of VEGF-mediated tip cell induction. Macrophages consequently play a hitherto unidentified and unpredicted part as vascular fusion cells. Moreover we show that we now have striking molecular commonalities between your pro-angiogenic tissues macrophages essential for vascular development and those that promote the angiogenic switch in cancer including the expression of the cell-surface proteins Tie up2 PD173074 and NRP1. Our findings suggest that cells macrophages are a target for antiangiogenic therapies but that they could equally well become exploited to stimulate cells vascularization in ischemic disease. Intro Blood vessels are essential for cells homeostasis in all vertebrates and fresh vessel growth termed neo-angiogenesis is definitely therefore a critical process in wound restoration ...

Endothelial progenitor cells (EPCs) were first isolated as CD34+ mononuclear cells (MNCs) from adult peripheral blood.1,2 Tissue ischemia mobilizes EPCs from bone marrow to peripheral blood, and mobilized EPCs home specifically to sites of nascent neovascularization and differentiate into mature endothelial cells (ECs).3 The demonstrated role of EPCs in the physiological response to ischemia has led to the development of strategies of cell therapy for neovascularization in ischemic diseases. Intravenous transplantation of cultured human EPCs enhances neovascularization and improves limb salvage in nude mice with hindlimb ischemia.4 A similar strategy applied in a model of myocardial ischemia in the nude rat demonstrated that transplanted human EPCs incorporated into rat myocardial neovascularization, differentiated into mature ECs in ischemic myocardium, enhanced neovascularization, preserved left ventricular (LV) function, and inhibited myocardial fibrosis.5 Recently, Kocher et al6 attempted ...

The Sox family is fundamental for organogenesis and many Sox members frequently cooperate. Sox members cooperate variously depending on the context: redundantly, sequentially, or complementarily. The KAIST team led by Injune Kim unveils a novel cooperation of Sox members for angiogenesis, new blood vessel formation.. This vascular biology team found that loss of any two copies of Sox7 and Sox17 genes in mouse embryo resulted in angiogenic defects, suggesting that Sox7 and Sox17 belonging to the SoxF subgroup genetically cooperates for developmental angiogenesis. VEGF, one of the most powerful stimulators of angiogenesis, upregulated both Sox7 and Sox17 in angiogenic endothelial cells. Both Sox7 and Sox17 increased VEGFR2, the VEGF receptor expressed in endothelial cells. Thus, these results demonstrate that Sox7 and Sox17 jointly promote developmental angiogenesis with overlapping expression and function.. Interestingly, VEGF regulation of SoxF expression and SoxF regulation of VEGFR2 expression ...

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Endothelial colony forming cells (ECFCs) were proved to take part in post-natal vasculogenesis and injury repair. The angiogenic properties of ECFCs could be influenced by various cytokines, chemokines, and growth factors. Erythropoietin (EPO) is a promising cytokine participating in angiogenesis. However, the mechanisms for EPOs proangiogenic effect still remain largely elusive. Here, we investigated the role of AMP-activated protein kinase (AMPK)-Krüppel-like factor 2 (KLF2) signaling pathway in the proangiogenic effect of EPO in ECFCs. Human ECFCs were isolated from cord blood and cultured. EPO significantly enhanced the migration and tube formation capacities of ECFCs and markedly increased the expression of endothelial markers and vascular endothelial growth factor (VEGF). Further, EPO caused the phosphorylation of AMPK and endothelial nitric oxide synthase (eNOS), in which process KLF2 was also up-regulated on both mRNA and protein levels. The up-regulation of KLF2 was blocked by ...

A growing population of patients who have exhausted current interventional and surgical approaches to treat coronary malperfusion depend on novel therapeutic approaches. One strategy potentially meeting the needs of the no option patient consists of therapeutic neovascularization via growth factors such as the vascular endothelial growth factor (VEGF), fibroblast growth factor, insulin-like growth factor (IGF), angiopoietin families among others. Earlier clinical studies using growth factor treatment of the ischemic region yielded mixed results, with singular studies improving the record by using advanced regional delivery (1,2) and vector (3) systems. The concept of therapeutic neovascularization requires angiogenesis (4), defined as capillary sprouting, as well as arteriogenesis (5,6) (e.g., enlargement of preexisting conductance vessels for improvement of tissue perfusion). Recent studies found a contribution of vasculogenesis (7,8)-using endothelial progenitor cells-to vessel growth in the ...

Figure 1. Schematic representation of secreted and membrane-bound MMPs and related ADAMs and ADAMTSs involved in angiogenesis. The proteins have various domains with specific functions in common. Key regulators of angiogenesis are indicated by the yellow squares. MT-MMP-1, -2, -3, and probably -5 enhance angiogenesis by their pericellular action (see Figure 4). Similarly MMP-2 and MMP-9 stimulate angiogenesis and can act pericellular by binding to membrane-anchored proteins. Pro-MMP-23 has a transmembrane domain, but this is removed during activation of the protease, making the active enzyme a soluble MMP. Part of the ADAM family members has proteolytic activity, of which ADAM-10,-15, and -17 are known to affect angiogenesis. ADAMTS-1 and the related ADAMTS-4 and -8 also can affect angiogenesis mainly via their thrombospondin (TSP) domains. The MMPs and MT-MMPs are depicted according to Sato50 with some modifications. ...

The data of the present article provide novel evidence that the class II HDAC9 is essential for angiogenic sprouting of endothelial cells in vitro and vessel formation in mice and zebrafish. The proangiogenic function of HDAC9 depends on its nuclear localization and the deacetylation domain, suggesting that HDAC9 transcriptionally controls angiogenesis-relevant genes. Indeed, HDAC9 represses the miR-17-92 cluster and thereby controls the expression of angiogenesis-relevant genes, such as Jak1.. The essential role of HDAC9 in angiogenesis was shown by several in vitro angiogenesis models and in vivo models. Silencing of HDAC9 profoundly reduced vascular growth of implanted human endothelial cells in vivo and disturbed vascular patterning in zebrafish. Furthermore, genetic deletion of HDAC9 impaired retinal vessel outgrowth and branching, as well as ischemia-induced neovascularization in mice. The function of HDAC9 is distinct from its close homolog HDAC5, which exhibits an antiangiogenic function ...

Postnatal neovascularization is the process of new blood vessel formation from preexisting endothelial cells.10 However, the origin of endothelial cells incorporated into the newly formed blood vessels has been the subject of intensive scrutiny. Emerging data have suggested that a subpopulation of BM-derived CEPs may contribute to new blood vessel formation.5 11 12 13 It has been shown that CEPs have the capacity of being recruited into ischemic tissues or growing tumors.4 13 14 15 In the present study, we have extended these observations by demonstrating that vascular trauma induces a very rapid but transient mobilization of a significant number of BM-derived VEGFR2+AC133+ cells.. Given the rapid entry of the CEPs into the peripheral circulation, it has been suggested that the chemocytokines released as a result of the vascular injury may induce mobilization of CEPs. Among the known chemocytokines, VEGF has been shown to be effective in mobilizing CEPs into the peripheral circulation.3 Indeed, ...

The SIRT1 deacetylase is the closest mammalian homologue of yeast Sir2, which regulates life span in response to caloric restriction. A previous study from our laboratory identified SIRT1 as a key regulator of endothelial angiogenic functions during blood vessel growth. To more precisely characterize the molecular nature of the defects in blood vessel formation associated with SIRT1 deficiency, we performed time lapse microscopy in SIRT1-deficient zebrafish embryos focusing on intersegmental vessel development using the tg(fli1:eGFP) line. Compared to the highly organized process of blood vessel development in the control embryos, we observed pathfinding defects and vascular regression in the SIRT1 zebrafish morphants due to dysregulated endothelial tip cell activity and a failure of endothelial stalk cells to maintain vessel growth. Conditional deletion of SIRT1 in the endothelial lineage of mice (Tie2Cretg;SIRT1flox/-) led to a remarkably similar vascular phenotype in the developing retina ...

TY - JOUR. T1 - Therapeutic angiogenesis. T2 - Protein and gene therapy delivery strategies. AU - Rosengart, Todd K.. AU - Patel, Shailen R.. AU - Crystal, Ronald. PY - 1999/1/1. Y1 - 1999/1/1. N2 - Angioplasty and surgical bypass, the primary interventional therapies for the treatment of atherosclerosis, are limited by the development over time of native vessel restenoses and graft occlusions. Furthermore, these therapies are not options for a significant number of individuals in whom the extent of vascular pathology is especially severe or widespread. Angiogenesis, the growth of new vasculature, is a critical biological response to ischemia that provides collateralization, or ‘biological revascularization’ of vascular obstructions. Therapeutic angiogenesis is a strategy whereby one of several known ‘angiogens’, mediators that induce angiogenesis, can be administered to augment the native angiogenic processes and enhance the formation of a collateral vasculature. This ...

In an experiment that could have applications in treating heart disease and strokes, researchers have taken certain cells from the blood and used them to grow entire networks of blood vessels in mice.. Whats really significant about our study is that we are using human cells that can be obtained from blood or bone marrow rather than removing and using fully developed blood vessels, said Harvards Joyce Bischoff, who led the study.[Reuters]. In the study, published in the journal Circulation Research [subscription required], researchers did not use controversial stem cells that can grow into any kind of specialized cell; they used the progenitor cells found in blood and bone marrow that can grow into several different types of cells. The progenitor cells were implanted in mice, and within seven days, a vigorous network of new vessels formed, joined up with the host animals blood vessels and started transporting blood [BBC News].. Researchers say the ability to grow extra blood vessels ...

A required role for MT1-MMP in neovessel formation, endothelial cell invasion, and collagenolytic activity. (A) Aortic vessel explants isolated from MT1-MMP-

In vitro cultures of endothelial cells are a widely used model system of the collective behavior of endothelial cells during vasculogenesis and angiogenesis. When seeded in a extracellular matrix, endothelial cells can form blood vessel-like structures, including vascular networks and sprouts. Endothelial morphogenesis depends on a large number of chemical and mechanical factors, including the compliancy of the extracellular matrix, the available growth factors, the adhesion of cells to the extracellular matrix, cell-cell signaling, etc. Although various computational models have been proposed to explain the role of each of these biochemical and biomechanical effects, the mechanisms underlying in vitro angiogenesis are still poorly understood. Most explanations focus on predicting the whole vascular network or sprout from the underlying cell behavior, and ignore the intermediate organizational levels of the system. Here we show, using a hybrid Cellular Potts and finite-element computational ...

Anti-VEGF treatments are a group of medicines which reduce new blood vessel growth or oedema (swelling). They can be used to treat a number of eye conditions which cause new blood vessel growth or swelling under the macula area of your retina.

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CANSSUFIVE is also based on the technology platform of angiogenesis screening assays. These unique assays screen for angiogenesis which is the process of new blood vessels formation from pre-existing blood vessels. Angiogenesis is an essential natural process in the body for healing and reproduction. The human body produces a precise balance of growth and inhibitory factors in healthy tissues to control angiogenesis. When this balance is altered, the result is either excessive or insufficient angiogenesis. The abnormal angiogenesis is a common denominator in many conditions including cancer, Alzheimers disease, diabetic blindness, wet age related macula degeneration, obesity and rheumatoid arthritis ...

The sprouting and development of blood vessels affects numerous processes in the body, and excessive or insufficient angiogenesis can exacerbate a variety of disease states. Therefore, precise regulation of angiogenesis is crucial to an organisms survival. Studies knocking down Dicer and Drosha implicated miRNAs in regulation of angiogenesis, and subsequent studies revealed roles for miR-126, the miR17~92 cluster, miR378, miR-210, miR-296, and others in various settings such as neoangiogenesis in response to injury, developmental angiogenesis, and tumor angiogenesis. (1, 5). Over the past year, significant progress has been made in discovering which miRNAs drive this process in both normal physiology and in various disease states. Due to these studies and others, a clearer picture of the miRNA network governing angiogenesis is starting to emerge. This review spans some of the most significant recent discoveries that have contributed to our understanding of angiomiR function in vascular ...

The formation of the vascular system begins in the embryo with the process of vasculogenesis, involving endothelial precursors known as angioblasts that give rise to a primitive network of simple endothelial cells defining tubes lacking a lumen. When the heart starts beating, the erythrocytes entry into the bloodstream establishes a circulation, and the developing vessels undergo morphological and functional changes. Meanwhile, the vasculature expands through angiogenesis, the process of vessel formation from pre-existing ones. Yet, this vascular network is just a rough draft that must undergo extensive remodeling to give rise to mature and stable vessels able to sustain a functional circulatory system. Changes in hemodynamic forces, as well as cellular processes, molecular signals, and metabolic rewiring drive vessel remodeling and maturation. Aberrant vessel growth and remodeling contribute to the pathogenesis of several human disorders. Extending our knowledge of the mechanisms governing vessel

Current therapies for ARMD and DR aim to inhibit cytokines that mediate the vasoproliferative response or to destroy the tissue that is creating the increased metabolic demand. A more rational therapeutic approach would be to relieve the hypoxia or to replace or normalize the cells that underlie the fibrotic response to injury. Our increased understanding of the angiogenic process has led to the identification of effector molecules, their cellular receptors, intracellular signaling cascades, and post-transcriptional regulators; this knowledge has translated into the use of compounds that can inhibit the pathological angiogenesis associated with tumors and neovascular eye diseases (90). Understanding of cell-cell and cell-ECM interactions that affect angiogenesis at the tissue level has also improved, and more recently a role for circulating cells in the regulation of vascular homeostasis in the adult organism has been identified in a number of organs, including the eye (91). In addition to the ...

Angiogenesis is the process of new blood vessel growth. In malignant tumors this process is essential for the delivery of needed nutrients and oxygen for the continued growth and survival of cancer cells. Thus the process of angiogenesis and the subsequent development of therapies that inhibit the process have generated great interest since Judah Folkmans original hypothesis

Results: In vitro and in vivo angiogenesis assays showed inhibition of capillary-like network formation of microvascular endothelial cells and neovascularization under dorsal skin of nude mice, respectively. We observed inhibition of intracerebral tumorigenesis and s.c. solid tumor formation in nude mice after treatment with combination of hTERT siRNA and IFN-γ. Western blotting of solid tumor samples showed significant downregulation of the molecules that regulate cell invasion, angiogenesis, and tumor progression ...

A team of investigators from the Argonne National Laboratory have identified a set of genes that might be responsible for cancer-related capillary formatio

Though zebrafish do not have placental arterioles and mice do not have a structural equivalent to the PAV, our developmental studies indicate that netrin signaling has evolved to ensure the formation of specific subsets of vessels. Thus, in contrast to VEGF signaling, which has profound effects on virtually all endothelial cells and vascular beds during developmental angiogenesis (Ferrara et al., 2003), guidance cues in general and UNC5B specifically, may provide an additional level of regulation to coordinate the spatial and temporal organization of tissue-specific vascular beds during embryogenesis. Because the first vital requirement for UNC5B is during mid-gestation, the reagents used in this study were unable to ascertain a function in later stages of development or within the adult. Such an assessment requires the use of alternative mutagenesis schemes, which we are vigorously pursuing.. A role for UNC5B in embryonic angiogenesis was originally postulated because of its vascular-specific ...

The spatial and temporal development of nascent capillary networks plays a major role in determining tissue patterning and function and it is important to understand how various cellular and molecular cues interact with migrating cells throughout angiogenic responses. The growth and differentiation of the mammalian neural retina-a process that depends upon the formation of a multi-layered, interconnected vascular supply-provides an excellent in vivo system for investigating angiogenesis and represents an exquisitely balanced objective for mathematical modelling.. The governing migratory mechanisms have been considered in a previously reported one-dimensional study of retinal angiogenesis [36]. However, this approach was, by definition, unable to generate spatial information for the entire retinal surface, and a more realistic two-dimensional hybrid PDE-discrete model has been derived here in order to track the migration of individual astrocyte and endothelial tip cells towards the outer retinal ...

Publications, Research Grants, Scientific Experts, Research Topics, Species, Genomes and Genes about physiologic neovascularization

Our angiogenesis assay, using iPSC-derived vascular endothelial cells, allows for the assessment of drug effects on blood vessel formation in disease.

Blood vessel growth; Sprouting angiogenesis; Computational modeling; Particle-continuum coupling; 3D; Matrix-bound VEGF; Extracellular matrix; ...

Using tumour models to study tumour angiogenesis is an advance on assays such as the CAM assay, as it allows study of the uptake and distribution of a drug

Nanoengineers at the University of California San Diego have 3D printed a lifelike, functional blood vessel network that could pave the way toward artificial organs and regenerative therapies.

Definition of angiogenic gene therapy in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is angiogenic gene therapy? Meaning of angiogenic gene therapy as a finance term. What does angiogenic gene therapy mean in finance?

Pericytes, surrounding the endothelium, fulfill diverse functions that are crucial for vascular homeostasis. The loss of pericytes is associated with pathologies, such as diabetic retinopathy and Alzheimers disease. Thus, there exists a need for an experimental system that combines pharmacologic manipulation and quantification of pericyte coverage during sprouting angiogenesis. Here, we describe an in vitro angiogenesis assay that develops lumenized vascular sprouts composed of endothelial cells enveloped by pericytes, with the additional ability to comparatively screen the effect of multiple small molecules simultaneously. For automated analysis, we also present an ImageJ plugin tool we developed to quantify sprout morphology and pericyte coverage. Human umbilical vein endothelial cells and human brain vascular pericytes were coated on microcarrier beads and embedded in fibrin gels in a 96-well plate to form lumenized vascular sprouts. After treatment with pharmacologic compounds, sprouts were fixed,

Peroxisome proliferator-activated receptor-γ (PPARγ) agonists, which have been used as insulin sensitizers in diabetic patients, may improve functions of endothelial cells (ECs). We investigated the effect of PPARγ on angiogenic activities of murine ECs and bone marrow-derived proangiogenic cells (PACs). PACs were isolated from bone marrow of 10-12 weeks old, wild type, db/db and PPARγ heterozygous animals. Cells were cultured on fibronectin and gelatin coated dishes in EGM-2MV medium. For in vitro stimulations, rosiglitazone (10 μmol/L) or GW9662 (10 μmol/L) were added to 80% confluent cell cultures for 24 hours. Angiogenic potential of PACs and ECs was tested in vitro and in vivo in wound healing assay and hind limb ischemia model. ECs and PACs isolated from diabetic db/db mice displayed a reduced angiogenic potential in ex vivo and in vitro assays, the effect partially rescued by incubation of cells with rosiglitazone (PPARγ activator). Correction of diabetes by administration of rosiglitazone

Primary Tumor Cell-derived endothelial cells can be used for a variety of purposes (e.g., assays of cell-cell adhesion, migration, vascular tube formation, angiogenesis assays and many other applications) Standard biochemical procedures can be performed using endothelial cell cultures include RT-PCR, Western blotting, immunoprecipitation, or immunofluorescent staining or flow cytometry, et al.. Primary Tumor Cell-derived endothelial cells from Cell Biologics are distributed for research purposes only. Our products are not authorized for human use. Transfer or resale of any Cell Biologics cells or products from the purchaser to other markets, organizations, or individuals is prohibited by Cell Biologics without the express written consent of the company. Cell Biologics Terms and Conditions must be accepted before submitting an order.. Question 9: How much does isolation of Tumor Cell-derived endothelial cells cost? ...

TY - JOUR. T1 - Combination of three angiogenic growth factors has synergistic effects on sprouting of endothelial cell/mesenchymal stem cell-based spheroids in a 3D matrix. AU - Kim, Sook Kyoung. AU - Lee, Jaeyeon. AU - Song, Myeongjin. AU - Kim, Mirim. AU - Hwang, Soon Jung. AU - Jang, Hwanseok. AU - Park, Yongdoo. PY - 2015. Y1 - 2015. N2 - Combinations of angiogenic growth factors have been shown to have synergistic effects on angiogenesis and natural wound healing in various animal models. Each growth factor has unique roles during angiogenesis; vascular endothelial growth factor (VEGF) plays a key role during the initial step of angiogenesis, whereas PDGF functions in the maturation of blood vessels. We used a combination of three angiogenic growth factors to increase angiogenesis in vitro and in vivo. We chose VEGF as a basic factor and added platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) to induce angiogenesis in three in vitro and in vivo models: 3D ...

Angiogenesis is critically reliant on endothelial cell-specific transcriptional mechanisms. rules and indicate that histone chaperones could be new focuses on for angiogenesis therapy. between days 8.5 and 9.0 (6) because of a lack of organized vasculature. Because deletion of the VEGFR1 tyrosine kinase website is compatible with normal vascular development (8), it appears that VEGFR1 functions like a decoy receptor for VEGFA during embryogenesis. However, several lines of evidence also suggest that function of VEGFR1 during angiogenesis is not limited to its VEGF trapping mechanism. Activation of VEGFR1 by VEGF induces migration of endothelial cells lacking VEGFR2 (9). VEGFR1 loss is definitely associated with decreased vascular sprout formation and vascular branching (10). This phenotype was also observed manifestation are mainly unfamiliar. Our earlier studies with mouse yolk sac endothelial cells (YSECs) and human being umbilical vein endothelial cells (HUVECs) showed that transcription is ...

Angiogenesis is an essential process whereby new blood vessels are formed from pre-existing vessels and occurs under both normal and pathophysiological conditions. growth element receptor 1 (sVEGFR-1). Therefore, FoxC1 appears to control angiogenesis by regulating two unique and opposing mechanisms; if so, vascular development could be identified, at least in part, Elvitegravir by a competitive balance between pro-angiogenic and anti-angiogenic FoxC1-controlled pathways. With this review, we describe the mechanisms by which FoxC1 regulates vessel growth and discuss how these observations could contribute to a more total understanding of the part of FoxC1 in pathological angiogenesis. Intro Under both physiological and pathological conditions, new blood vessels are created from pre-existing vessels through a process called angiogenesis, which is definitely exactly controlled by the balance between pro-angiogenic and anti-angiogenic factors. Vascular endothelial growth element (VEGF)-A is perhaps ...

TY - JOUR. T1 - Pravastatin-induced proangiogenic effects depend upon extracellular FGF-2. AU - Shiota, Masayuki. AU - Hikita, Yuko. AU - Kawamoto, Yukiko. AU - Kusakabe, Hiromi. AU - Tanaka, Masako. AU - Izumi, Yasukatsu. AU - Nakao, Takafumi. AU - Miura, Katsuyuki. AU - Funae, Yoshihiko. AU - Iwao, Hiroshi. PY - 2012/9. Y1 - 2012/9. N2 - The HMG-CoA reductase inhibitors (statins) have been shown to exert several protective effects on the vasculature that are unrelated to changes in the cholesterol profile, and to induce angiogenesis. The proangiogenic effect exerted by statins has been attributed to the activation of the PI3K/Akt pathway in endothelial cells; however, it is unclear how statins activate this pathway. Pravastatin-mediated activation of Akt and MAPK occurs rapidly (within 10 min.) and at low doses (10 nM). Here, we hypothesized that FGF-2 contributes to the proangiogenic effect of statins. We found that pravastatin, a hydrophilic statin, induced phosphorylation of the FGF ...

Here we showed that Foxo1 is expressed in developing embryonic vasculature and complete disruption of Foxo1 resulted in embryonic lethality due to vascular defects. Thus, Foxo1 is an essential regulator in embryonic vessel formation. Formation of the embryonic vasculature has been separated into two major processes, vasculogenesis and angiogenesis (23). During the initial stages of vascular development, endothelial cell precursors form a network of homogeneous and primitive blood vessels (the primary vascular plexus) by the process of vasculogenesis. The primary vascular plexus is then remodeled through the process of angiogenesis by sprouting and pruning blood vessels and recruiting mural cells to establish the vascular structure. In Foxo1-null mutant embryos, vasculature stained by PECAM-1 can be seen at E9.5, although it is immature compared to wild-type embryos. This finding suggests that Foxo1 may not have a major role in the process of embryonic vasculogenesis. However, the failure to ...

TY - JOUR. T1 - Stereolithographic modeling of the deep circumflex iliac artery and its vascular branching. T2 - A further advance in computed tomography-guided flap planning. AU - Rozen, Warren M.. AU - Ting, Jeannette W.C.. AU - Baillieu, Charles. AU - Leong, James. PY - 2012/8. Y1 - 2012/8. UR - http://www.scopus.com/inward/record.url?scp=84864971986&partnerID=8YFLogxK. U2 - 10.1097/PRS.0b013e31825903d1. DO - 10.1097/PRS.0b013e31825903d1. M3 - Comment / Debate. VL - 130. JO - Plastic and Reconstructive Surgery. JF - Plastic and Reconstructive Surgery. SN - 0032-1052. IS - 2. ER - ...

Basement matrices such as Matrigel™ and Geltrex™ are used in a variety of cell culture assays of anchorage-dependent differentiation including endothelial cell tube formation assays. The volumes of matrix recommended for these assays (approximately 150 μl/cm2) are costly, limit working distances for microscopy, and require cell detachment for subsequent molecular analysis. Here we describe the development and validation of a thin-layer angiogenesis (TLA) assay for assessing the angiogenic potential of endothelial cells that overcomes these limitations. Geltrex™ basement matrix at 5 μl/cm2 in 24-well (10 μl) or 96-well (2 μl) plates supports endothelial cell differentiation into tube-like structures in a comparable manner to the standard larger volumes of matrix. Since working distances are reduced, high-resolution single cell microscopy, including DIC and confocal imaging, can be used readily. Using MitoTracker dye we now demonstrate, for the first time, live mitochondrial dynamics and

Primary endothelial cells can be used for a variety of purposes (e.g., assays of cell-cell adhesion, migration, vascular tube formation, angiogenesis assays and many other applications) Standard biochemical procedures can be performed using endothelial cell cultures include RT-PCR, Western blotting, immunoprecipitation, or immunofluorescent staining or flow cytometry, et al.. Primary endothelial cells from Cell Biologics are distributed for research purposes only. Our products are not authorized for human use. Transfer or resale of any Cell Biologics cells or products from the purchaser to other markets, organizations, or individuals is prohibited by Cell Biologics without the express written consent of the company. Cell Biologics Terms and Conditions must be accepted before submitting an order.. Question 10: How much does isolation of endothelial cells cost? ...

ABSTRACT. Vascular formation in vivo involves several processes and signal cascades subsequently occurring in the embryo. Several models by ES cells have been reported for analysis in vitro. We show here a 3D culture system using collagen gel (AteloCell) as a simple and useful system for investigating vascular formations and analyzing the roles of factors in vivo. Although VEGF and PDGF are growth factors with multi-potentials for vascular formation, their sequential roles have not been elucidated. We investigated the effects of VEGF and PDGF B signals for vascular formation by a 3D culture system that embedded embryoid bodies (EBs) from ES cells into a collagen gel. After embedding EBs in the collagen gel with a medium containing VEGF, EBs gave off CD105 immunopositive vessels as the initial step of vasculogenesis. When the factor in the culture medium for EBs was switched from VEGF to PDGF B after 5 days of culture, the morphological features of vessels varied, suggesting the occurrence of ...

TY - JOUR. T1 - Homeobox D1 regulates angiogenic functions of endothelial cells via integrin β1 expression. AU - Park, Hyojin. AU - Choi, Hyun Jung. AU - Kim, Jihye. AU - Kim, Minhyung. AU - Rho, Seung Sik. AU - Hwang, Daehee. AU - Kim, Young Myeong. AU - Kwon, Young Guen. PY - 2011/4/29. Y1 - 2011/4/29. N2 - Homeobox (HOX) family genes, major transcription factors for embryonic development, have been also implicated in vascular development and angiogenesis, particularly with regulation of genes involved in cell-cell or cell-extracellular matrix (ECM) interactions. However, the cellular and molecular functions of HOXD1 in endothelial cells (ECs) are yet to be explored. We here report that HOXD1 is prominently expressed in human ECs and regulates angiogenic activities. Knockdown of HOXD1 in ECs resulted in significant inhibition of migration and adhesion as well as tube like structure formation. These effects were correlated with the reduced expression of integrin β1 (ITGB1), an important ...

We have previously demonstrated that mesenchymal stem cells (MSC), when injected into rodent hearts following myocardial infarction (MI), enhance myocardial rep...

Three dimensional time-lapse imaging is time-consuming and labor intensive, but the resulting data provide rich dynamic information that may yield new insights into mechanisms of growth and development. Analysis of developmental dynamics does not replace but augments standard morphometric analyses. Our new method is useful not only for analysis of angiogenic sprouting in zebrafish, but also for analysis of angiogenic sprouting in other systems and for other similar events such as analysis of neurite growth dynamics in axonal pathfinding.. Automated extraction of meaningful information from digital images is a complex problem because time-lapse data acquired from living organisms frequently has a low signal and high noise. The human visual cortex is excellent for extracting information from such images but cannot yet be entirely replaced by computer vision. We tested software tools in FIJI ImageJ and in IMARIS that refined manually selected points to a nearby point of local maximum signal ...

There is a growing body of evidence on the importance of hemodynamic forces (i.e. blood flow and pressure) in regulating endothelial cell behavior and blood vessel formation. I was part of a recent discovery published in Nature Cell Biology that identified a new type of membrane protrusion-called inverse blebbing-at the apical membrane of endothelial cells. These inverse blebs drive the expansion of the lumen, which is a structure that allows blood to flow through the vessels. This process is therefore important in the formation of functional blood vessels ...

Scientists have discovered that cotton candy may help grow replacement tissue. It can be used for making networks of blood vessels in laboratory grown skin, muscle, bone or fat. Dr. Jason Spector of Cornell Medical Center in New York and Leon Bellan of Cornell University presented their research in a paper for Soft Matter. A thick liquid chemical is poured over a chunk of the sugary stuff. After it solidifies, it is placed in warm water to dissolve the candy. What is left is a piece of material with tiny channels which are lined with cells to create the blood…

There has been little work on the regulation of adipose tissue angiogenesis in obese subjects, although evidence implicates angiogenesis in the development of adipose tissue. Our study shows that adipose tissue from obese adult subjects grafted on CAM was able to induce angiogenesis with recruitment of vascular cells of both human and host (avian) origin. Although the expression of several angiogenic genes differed slightly between SAT and VAT, the expression of the main angiogenic factors, and notably VEGF, was similar in SAT and VAT. SAT and VAT also had similar angiogenic potencies on CAM, and inhibition of VEGF strongly inhibited angiogenesis in both tissues.. Adipose tissue is highly vascularized (2,3,5,9), and many angiogenic factors are secreted by adipose tissue, including VEGF, hepatocyte growth factor, placental growth factor (PlGF), angiopoietins, FGFs, TNF-α, PAI-1, and metalloproteases (2,8,9,18,32,33). Adipose tissue contains mature adipocytes and many other cell types known as ...

Im very excited on starting a new phase and new treatment approach. I have been searching on how to increase angiogenesis or blood vessel formation in the scalp. VEGF is one thing that increases that and there are several pathways that are involved in ang

Coordination between the vascular system and forming organs is essential for proper embryonic development. The vasculature expands by sprouting angiogenesis, during which tip cells form filopodia that incorporate into capillary loops. Although several molecules, such as vascular endothelial growth factor A (Vegfa), are known to induce sprouting, the mechanism that terminates this process to ensure neovessel stability is still unknown. Sphingosine-1-phosphate receptor 1 (S1P1) has been shown to mediate interaction between endothelial and mural cells during vascular maturation. In vitro studies have identified S1P1 as a pro-angiogenic factor. Here, we show that S1P1 acts as an endothelial cell (EC)-autonomous negative regulator of sprouting angiogenesis during vascular development. Severe aberrations in vessel size and excessive sprouting found in limbs of S1P1-null mouse embryos before vessel maturation imply a previously unknown, mural cell-independent role for S1P1 as an anti-angiogenic factor. ...

INTRODUCTION Stimulation of coronary collateral vessel growth by therapeutic angiogenesis (TA) offers an alternative treatment option for patients with refractory angina. Several TA modalities, including delivery to the heart of angiogenic growth factors (proteins or genes) and cells have been tested in clinical trials in the past two decades, but so far none of them resulted in significant therapeutic efficacy in large scale studies. This review attempts to identify the main obstacles hindering clinical success and recommends measures to overcome them in the future. AREAS COVERED After stating the medical need and rational for TA, and listing and briefly discussing past and current TA clinical trials, three main areas of obstacles are described: conceptual questions, technical limitations and clinical design uncertainties. Based on scientific and technical advances and lessons learned in past clinical trials, potential solutions to overcome some of these obstacles are proposed. EXPERT OPINION

Endothelial tubulogenesis is a crucial step in the formation of functional blood vessels during angiogenesis and vasculogenesis. Here, we use in vivo imaging of living zebrafish embryos expressing fluorescent fusion proteins of beta-Actin, alpha-Catenin, and the ERM family member Moesin1 (Moesin a), to define a novel cord hollowing process that occurs during the initial stages of tubulogenesis in intersegmental vessels (ISVs) in the embryo. We show that the primary lumen elongates along cell junctions between at least two endothelial cells during embryonic angiogenesis. Moesin1-EGFP is enriched around structures that resemble intracellular vacuoles, which fuse with the luminal membrane during expansion of the primary lumen. Analysis of silent heart mutant embryos shows that initial lumen formation in the ISVs is not dependent on blood flow; however, stabilization of a newly formed lumen is dependent upon blood flow. Zebrafish moesin1 knockdown and cell transplantation experiments demonstrate ...

One of the key challenges in the field of blood vessel engineering is the in vitro production of small and large diameter vessels. Considering that a combi

New blood vessel growth, or angiogenesis, is critical for cancer to grow and spread throughout the body. Drugs that target vascular endothelial growth factor -- a key driver of angiogenesis -- are now approved for the treatment of several metastatic cancers. However, not all patients respond and many more eventually become resistant after initial treatment benefits.

Angiogenesis, the process of new blood vessel formation from existing vessels, plays an important role in normal physiology (Tonnesen et al., 2000), as well as in many pathological conditions including cancer (Folkman, 1971; Papetti and Herman, 2002), macular degeneration (Ahmad et al., 2011), and various vascular diseases (Khurana et al., 2005). Strikingly, increased angiogenesis is observed in many types of human cancers (Bergers and Benjamin, 2003; Dvorak, 2003), whereas angiogenesis is decreased in age-associated vascular diseases (Ungvari et al., 2010). Therefore, diseases that are associated with increased angiogenesis, such as human cancers, can be treated by inhibiting angiogenesis (Folkman, 2007). In contrast, stimulation of angiogenesis could be beneficial in the treatment of coronary artery disease and other vascular diseases characterized by insufficient blood flow to target organs as a result of blocked or damaged blood vessels (Khan et al., 2002; Al Sabti, 2007). Many factors that ...

Tissue branching morphogenesis requires the hierarchical organization of sprouting cells into leading tip and trailing stalk cells [ [1] and [2]]. During new blood vessel branching (angiogenesis), endothelial tip cells (TCs) lead sprouting vessels, extend filopodia, and migrate in response to gradients of the secreted ligand, vascular endothelial growth factor (Vegf) [3]. In contrast, adjacent stalk cells (SCs) trail TCs, generate the trunk of new vessels, and critically maintain connectivity with parental vessels. Here, we establish that h2.0-like homeobox-1 (Hlx1) determines SC potential, which is critical for angiogenesis during zebrafish development. By combining a novel pharmacological strategy for the manipulation of angiogenic cell behavior in vivo with transcriptomic analyses of sprouting cells, we identify the uniquely sprouting-associated gene, hlx1. Expression of hlx1 is almost entirely restricted to sprouting endothelial cells and is excluded from adjacent nonangiogenic cells. ...

Abstract.It takes two to make blood vessels-endothelial cells and pericytes. While the endothelial cells are the better characterized of the two, pericytes are now coming into focus as important regulators of angiogenesis and blood vessel function, and as potential drug targets. However, pericytes are still surrounded by much controversy. They are difficult to define, they constitute a heterogeneous population of cells, and their ontogeny is not well understood. They are plastic and have the capacity to differentiate into other mesenchymal cell types, such as smooth muscle cells, fibroblasts and osteoblasts. Recent interest in pericytes also stems from their potential involvement in diseases such as diabetic microangiopathy, tissue fibrosis, cancer, atherosclerosis and Alzheimers disease. The present review focuses on the role of pericytes in physiological angiogenesis. The currently favored view states that the initial endothelial tubes form without pericyte contact, and that subsequent acquisition of

Vascular networks are central to the functioning of most tissues. We use a two-cell approach to bioengineer human vascular networks in vivo. In our model, human blood-derived ECFCs are combined with human Mesenchymal Stem Cells (MSCs) in a biocompatible hydrogel and injected subcutaneously into immunodeficient mice where they form an organized vascular network that joins with the mouse vasculature. This model is ideally suited for studies on the cellular and molecular mechanisms of human vascular network formation and for developing strategies to vascularize tissues. ...

Angiogenesis is a multicellular morphogenesis process that expands vascular networks in tissue. Various biological components concertedly contribute to angiogenic morphogenesis. The most important cellular component is endothelial cells, which we use to reconstruct 3D angiogenic process in a extracellular matrix in response to angiogenic growth factors. In addition, perivascular pericytes, blood flow and extravascular tissue importantly serve as (sub)components that allow constructing more sophisticated vascular networks. However, a mechanistic understanding of how the individual components contribute to various angiogenic processes is largely missing. In this seminar, I will introduce a reconstitution angiogenesis assay system with a microfluidic device that allows dissecting the phenomenon in a bottom-up way by adding individual components to the essential one. I will discuss the roles of pericyte and intraluminal pressure on angiogenic morphogenesis based on recent unpublished data obtained ...

The ECM protein Del-1 is one of several novel ECM proteins that accumulate around angiogenic blood vessels in embryonic and tumor tissue and promote angiogenesis in the absence of exogenous growth factors. Del-1 expressed in mouse or rabbit ischemic hind-limb muscle by gene transfer rapidly promotes new blood vessel formation and restores muscle function. This angiogenic ECM protein initiates angiogenesis by binding to integrin αvβ5 on resting endothelium, thereby resulting in expression of the transcription factor Hox D3 and integrin αvβ3. Hox D3 converts resting endothelium to angiogenic endothelium by inducing expression of proangiogenic molecules such as integrin αvβ3. These findings provide evidence for an angiogenic switch that can be initiated in the absence of exogenous growth factors and indicate that the angiogenic matrix protein Del-1 may be a useful tool for the therapy of ischemic disease.. ...

The formation of new blood vessels is a complex multistep process. Endothelial cells resting in the parent vessels are activated by an angiogenic signal and stimulated to synthesize and release degradative enzymes, allowing endothelial cells to migrate, proliferate, and finally, differentiate to give rise to capillary tubules. Any of these steps may be a potential target for pharmacologic intervention (3). IB05204 antiangiogenic activity was firstly detected using the in vitro differentiation assay for endothelial cells. Our results show that IB05204 completely inhibits capillary-like tube formation by BAEC or HUVEC at concentrations (2 and 5 μmol/L, respectively) that are lower than those required for endothelial proliferation inhibition (IC50 = 14 and 17 μmol/L for BAEC and HUVEC, respectively). Furthermore, IB05204 antiproliferative effect does not seem to be endothelial cell specific because these IC50 values are similar or even higher to those obtained with tumor cells (IC50 = 4.2, and ...

During angiogenesis, the protein prohibitin-1 doesnt live up to its name. Instead of stopping some cellular process, it encourages new blood vessel growth by ensuring that mitochondria run efficiently, as Schleicher et al. reveal.. For lower organisms, prohibitin-1 is an asset. It keeps mitochondria functioning smoothly, and its loss pushes cells into the low-activity, slow-dividing state called senescence. The researchers suspected that prohibitin-1 would do a similar job in mammals and might be particularly important for vascular homeostasis, since mitochondrial maintenance is known to be important for vascular health-reactive oxygen species (ROS) that spill out from malfunctioning mitochondria can damage endothelial cells and prompt atherosclerosis.. The team knocked down the protein in mammalian endothelial cells and found that the cells ROS levels shot up and several signs of senescence became apparent. Without the protein, cells also moved less and wouldnt roll up into tubes, suggesting ...

DESCRIPTION (provided by applicant): The reduction of oxygen occurring as a result of advanced vascular diseases poses severe clinical problems including massive cell death and resultant tissue loss. Compared to pharmacological methods of therapeutic angiogenesis, cell-based strategies represent a direct approach to generate a capillary network. Endothelial colony forming cells (ECFCs) are a subpopulation of endothelial progenitor cells that exhibit robust angiogenic potential under hypoxic conditions and can form functional vascular networks in vivo. Adipose- derived stem cells (ASCs) are a promising cell population for promoting angiogenesis and potentially stabilizing new vessels. However, the success of cell-based therapies is limited by rapid cell death due to apoptosis upon implanting cells into ischemic tissue environments, dramatically reducing the number of cells available to participate in vasculogenesis. Additionally, recent data suggest that cells derived from older donors are more ...

OBJECTIVE:Stem cell-based regenerative therapies have been intensively studied with the aim to define an ideal cell type for the treatment of myocardial infarction. We tested systemically delivered, platelet-targeted induced vascular progenitor cells (iVPCs) to study their potential to salvage damaged myocardium after ischemia-reperfusion injury. METHODS:Using a mouse model of ischemia-reperfusion injury, we tested the potential of platelet-targeted iVPCs (1 × 106 targ-iVPCs) compared to non-targ-iVPCs and a saline control. Bioluminescence imaging, echocardiography, and histological analyses were performed. RESULTS:Four weeks after ischemia-reperfusion injury, systemic delivery of targ-iVPCs led to reduced fibrosis and infarct size (PBS: 25.7 ± 3.9 vs targ-iVPC: 18.4 ± 6.6 vs non-targ-iVPC: 25.1 ± 3.7%I/LV, P < 0.05), increased neovascularization, and restored cardiac function (PBS: 44.0 ± 4.2 vs targ-iVPC: 54.3 ± 4.5 vs non-targ-iVPC: 46.4 ± 3.8%EF, P < 0.01). Cell tracking experiments ...

The outgrowth of new blood vessels from pre-existing vessels, called angiogenesis, is a crucial step in many physiological and pathological mechanisms, including wound healing and tumor growth. Angiogenesis is a topic of intensive experimental investigation so its phenomenology and many of the molecular signals contributing to it have been well characterized. Yet it is poorly understood how the biological components fit together dynamically to drive the outgrowth of blood vessels. Cell-based simulation models help analyze how cells assemble into embryonic structures, and how cell behavior is guided by signals from neighboring cells. With such cell-based simulation models, we have identified dynamic cell behaviors by which endothelial cells can form sprouts from existing blood vessels. In one of these, endothelial cells secrete a chemoattractant that attracts other endothelial cells. By itself this mechanism causes cells to aggregate into isolated clusters. But including experimentally observed ...

In the circulatory system, while larger features of the vasculature such as arteries and veins appear to be statically positioned for years of use, finer features in the human body and in biology relates to a continuous branching out of a circulatory network that is required for tissue growth. This process is related to biochemical pathways and is vital to be understood so that issues in health and disease can be better addressed. Angiogenesis is the formation of new blood vessels from existing vessels. A functional vascular network is established by balanced angiogenesis processes. While the activation of angiogenesis extends vascular networks crucial for tissue growth, angiogenic vessels should be stabilized to undertake necessary vascular functions. The Notch pathway is fundamental for allowing for vascular stabilization. It acts by preventing excessive angiogenesis. However, how this signaling pathway that is conserved in various biological processes can induce changes that are ...

Ebba Brakenhielm is an Editor at PeerJ. Bio: INSERM Tenured Researcher in the field of Cardiovascular Research, currently focusing on therapeutic angiogenesis with polymer-based targeted growth factor delivery. PhD in Tumor Biology (Pr Yihai Cao, Karolinska Institutet, Sweden), and expertise in Adipose tissue angiogenesis. Postdoc at UCLA (Pr Lily Wu) in molecular imaging and tumor lymphangiogenesis field. Member of European Vascular Biology Organisation, French society for Cardiovascular Research, French society for Angiogenesis Research.

The role of endothelial progenitor cells (EPCs) on vascular repair and neovasculogenesis is impaired in diabetes. This study aimed to investigate the effect of N-epsilon-carboxymethyl lysine (CML) on caspase-3 expression and morphology of early EPCs. After 7 days of culturing, primary cultures of early EPCs were randomly divided into four groups. One group is a normal group. Three groups were exposed to low (50 g/ml), medium (100 g/ml), and high (200 g/ml) doses of CML for an hour. The caspase-3 expression and morphology of early EPCs were evaluated by laser scanning confocal microscope. The caspase-3 expression of early EPCs increased in groups exposed to low and medium dose of CML, and decreased in group exposed to high dose of CML compared to normal. Exposure of CML changed the morphology of early EPCs including cells shrinkage, unclear margin between cytoplasm and nucleus, also oval-shape cells. Given that CML may contribute to the functional defects of the endothelium in diabetes by causing ...