Coating of Polystyrene Surface with REDV-Gelatin Conjugate for Selective Isolation of Endothelial Cells

2021 ◽  
Vol 904 ◽  
pp. 287-292
Author(s):  
Wan Song Zhang ◽  
Ya Jie Fu ◽  
Rui Wang ◽  
Xuan Hui Qiu ◽  
Ze Yuan Feng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Function ◽  
Flow Cytometric Analysis ◽  
Internal Surface ◽  
Cost Effective ◽  
Cell Viability Assay ◽  
Simple Method ◽  
Migration Assay ◽  
Gelatin Coating

Endothelial cells (EC), which line the internal surface of blood vessels, play various essential roles in controlling vascular function. The mouse is an important animal model for the study of vascular biology and cardiovascular diseases. However, the isolation of primary EC from the murine aorta is challenging because they are readily contaminated by smooth muscle cells (SMC). A previous study developed a simple method to isolate murine EC from SMC. By taking advantage of the differential sedimentation rate between the two cells, the EC was selectively enriched with collagen-coated polystyrene surfaces. Our study further improved this method by introducing a biomimetic peptide REDV (Arg-Glu-Asp-Val), which may bind specifically to EC but not to SMC or fibroblasts. Firstly, REDV-gelatin conjugate was synthesized by using the amine-to-sulfhydryl crosslinker SMCC. REDV-gelatin coating was then prepared on polystyrene surfaces, and their affinities to EC and SMC were subsequently investigated. Fluorescence microscopy and flow cytometric analysis showed that EC adhesion to the gelatin coating was significantly promoted by REDV peptide conjugation. Moreover, cell migration assay and cell viability assay also showed that the conjugation of REDV does not affect EC migration, and this coating did not show cytotoxicity against EC. This gelatin-REDV coating provides a cost-effective and straightforward tool for isolating EC from SMC, which may facilitate in vitro investigations of EC from mice.

scholarly journals Crocodile blood supplementation protects vascular function in diabetic mice

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Chui Yiu Bamboo Chook ◽  
Francis M. Chen ◽  
Gary Tse ◽  
Fung Ping Leung ◽  
Wing Tak Wong
Keyword(s):  
Endothelial Cells ◽  
Vascular Function ◽  
Quantitative Polymerase Chain Reaction ◽  
Functional Study ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Gene Expressions ◽  
Inflammatory State ◽  
Crocodile Blood

Abstract Cardiovascular disease is a major cause of mortality in diabetic patients due to the heightened oxidative stress and pro-inflammatory state in vascular tissues. Effective approaches targeting cardiovascular health for diabetic patients are urgently needed. Crocodile blood, an emerging dietary supplement, was suggested to have anti-oxidative and anti-inflammatory effects in vitro, which have yet to be proven in animal models. This study thereby aimed to evaluate whether crocodile blood can protect vascular function in diabetic mice against oxidation and inflammation. Diabetic db/db mice and their counterparts db/m+ mice were treated daily with crocodile blood soluble fraction (CBSF) or vehicle via oral gavage for 4 weeks before their aortae were harvested for endothelium-dependent relaxation (EDR) quantification using wire myograph, which is a well-established functional study for vascular function indication. Organ culture experiments culturing mouse aortae from C57BL/6 J mice with or without IL-1β and CBSF were done to evaluate the direct effect of CBSF on endothelial function. Reactive oxygen species (ROS) levels in mouse aortae were assessed by dihydroethidium (DHE) staining with inflammatory markers in endothelial cells quantified by quantitative polymerase chain reaction (qPCR). CBSF significantly improved deteriorated EDR in db/db diabetic mice through both diet supplementation and direct culture, with suppression of ROS level in mouse aortae. CBSF also maintained EDR and reduced ROS levels in mouse aortae against the presence of pro-inflammatory IL-1β. Under the pro-inflammatory state induced by IL-1β, gene expressions of inflammatory cytokines were downregulated, while the protective transcripts UCP2 and SIRT6 were upregulated in endothelial cells. Our study suggests a novel beneficial effect of crocodile blood on vascular function in diabetic mice and that supplementation of diet with crocodile blood may act as a complementary approach to protect against vascular diseases through anti-oxidation and anti-inflammation in diabetic patients. Graphical abstract

scholarly journals Immobilized DNA aptamers used as potent attractors for vascular endothelial cell: in vitro study of female rat

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Jung-Joon Cha ◽  
Hoyeon Lee ◽  
Miyoung Kim ◽  
Juyoung Kang ◽  
Hanlim Song ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Function ◽  
Therapeutic Potential ◽  
Vascular Endothelial Cells ◽  
Specific Binding ◽  
Vascular Endothelial Cell ◽  
Dna Aptamers ◽  
Female Rat ◽  
Vascular Endothelial

Abstract Vascular endothelial cells are essential to vascular function and maintenance. Dysfunction of these cells can lead to the development of cardiovascular disease or contribute to tumorigenesis. As such, the therapeutic modulation and monitoring of vascular endothelial cells are of significant clinical interest, and several endothelial-specific ligands have been developed for drug delivery and the monitoring of endothelial function. However, the application of these ligands has been limited by their high cost and tendency to induce immune responses, highlighting a need for alternate methods of targeting vascular endothelial cells. In the present study, we explore the therapeutic potential of DNA aptamers. Using cell-SELEX technology, we identified two aptamers with specific binding affinity for vascular endothelial cells and propose that these molecules show potential for use as new ligands for drug and biomarker research concerning vascular endothelial cells.

P13.08 Novel Thioridazine derivates: Antiproliferative and apoptosis-inducing activity on glioblastoma cells in vitro

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii34-ii34
Author(s):  
S G Schwab ◽  
K Sarnow ◽  
E Alme ◽  
R Goldbrunner ◽  
H Bjørsvik ◽  
...  
Keyword(s):  
Imaging System ◽  
Therapeutic Potential ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Therapeutic Effects ◽  
Cell Viability Assay ◽  
Selective Cytotoxicity ◽  
Viability Assay

Abstract BACKGROUND Although withdrawn from the market due to cardiotoxicity, we have shown that the antipsychotic drug Thioridazine shows chemosensitizing effects in combination with Temozolomide (TMZ) for the treatment of glioblastoma multiforme (GBM). Based on our prior observations, the aim of the presented project was through medicinal chemistry, to design and synthesize new compounds based on Thioridazines tricyclic structure, and to determine their therapeutic potential. MATERIAL AND METHODS Fourteen compounds were synthesized where variations were made within the tricyclic side chains. The newly synthesized compounds were screened for therapeutic efficacy with or without TMZ using a WST-1 cell viability assay as well as a real-time imaging system (IncuCyte). Tests were performed on both monolayer cell cultures, as well as on glioma stem cell spheroids (GSC). The therapeutic effects were also studied on human astrocytes (NHA) as well as on rat brain organoids (BO). Annexin V/propidium iodide (PI) double staining followed by flow cytometric analysis was performed after 48 hours of treatment. RESULTS Following an extensive screening, we identified two novel compounds (EA01 and EA02) that at concentrations of 4 and 9.5 µM showed a strong cytotoxicity on GBM cell lines (U-87 MG p<0,0001, U251 p<0,0001, LN18 p=0,0004) as well as on glioma stem cells (GSC) (P3 p<0,0001) compared to NHA and BOs respectively. Also, when BOs were confronted with GSC spheres in an invasion assay, a selective cytotoxicity was observed in the GSCs. Mechanistically, we show that both compounds induce apoptosis in the GBM cells. Moreover, intravenous delivery of increasing concentrations of EA01 and EA02 revealed no toxicity in animals at concentrations up to 21 mg/kg. CONCLUSION We have developed two new tricyclic therapeutic compounds that show a strong selective cytotoxicity in GBM cells with limited systemic toxicity in animals. Ongoing studies are investigating the therapeutic potential of EA01 and EA02 in orthotopic xenografts in vivo.

miR-208a-3p promotes NSCLC proliferation and migration by suppressing lncRNA-MEG3 expression

2021 ◽  
Author(s):  
Linfei Yang ◽  
Qian Li ◽  
Hai Zhong ◽  
Liang Ye ◽  
Surong Fang ◽  
...  
Keyword(s):  
Protein Extraction ◽  
Underlying Mechanism ◽  
In Vitro Assays ◽  
Cell Viability Assay ◽  
Migration Assay ◽  
Normal Tissues ◽  
Viability Assay ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background The disordered expression of maternally expressed gene 3 (MEG3) has been observed in non-small-cell lung cancer (NSCLC). However, the molecular mechanism accounting for this abnormal expression is not fully understood. Methods MEG3 expression was detected by qRT-PCR in 51 cases of NSCLC and adjacent normal tissues. Then, the relationship between MEG3 and miR-208a-3p was assessed in vitro by cell viability assay, cell migration assay, protein extraction and western blot analysis. Resoults We observed that MEG3 expression was decreased in NSCLC tissues. And MEG3 expression was negatively related to lymph node metastasis and differentiation. Moreover, MEG3 expression is regulated by miR-208a-3p expression by overexpression and knockout experiments. Furthermore, we focused on the underlying mechanism of MEG3 downregulation. We found that the overexpression of miR-208a-3p reduced the level of MEG3 expression based on computational predictions and in vitro assays. Using CCK-8 and transwell migration assays, we found that the overexpression of miR-208a-3p can increased proliferation and apoptosis in NSCLC cells. Moreover, the depletion of MEG3 rescued the proliferation and migration induced by miR-208a-3p knockdown. Conclusion Taken together, the results of this study reveal that miR-208a-3p promotes NSCLC tumorigenesis by negatively regulating MEG3 expression and functions as an oncogenic miRNA in NSCLC.

Abstract 17225: Extracellular Signal-Regulated Kinase 1/2 is Essential for Lipocalin-2 Signaling in Endothelial Cells

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Markus Theurl ◽  
Andrea Schroll ◽  
Igor Theurl ◽  
Daniela Lener ◽  
Wolfgang-Michael Franz ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Function ◽  
Umbilical Vein ◽  
Brdu Incorporation ◽  
Lipocalin 2 ◽  
Vascular Disorders ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Stimulation Of

Introduction: Lipocalin-2 (Lcn2) is an acute phase protein and a marker of kidney injury. Recently, elevated Lcn2-levels have been reported in heart failure and myocardial infarction. Moreover, stimulation of breast cancer angiogenesis was observed. Thus, we hypothesized that Lcn2 may be a regulator of vascular function and a target for the treatment of ischemic vascular disorders. Methods/Results: In-vitro Lcn2 mediated proliferation of human umbilical vein endothelial cells (HUVEC; rel. proliferation Lcn2 10 nM vs. ctr.: 1.4±0.09, n=3, P<0.001) and human coronary artery endothelial cells (HCAEC; rel. proliferation Lcn2 10 nM vs. ctr.: 1.3±0.07, n=3, P<0.01) as determined by BrdU-incorporation. In the in-vitro matrigel assay stimulation of HUVEC (1.4 fold vs. ctr., n=3, P<0.01) and HCAEC (1.6 fold vs. ctr., n=3, P<0.001) with Lcn2 resulted in a significant induction of capillary like tube formation. All effects were similar to vascular endothelial growth factor (VEGF). Mechanistically these results can be traced back to phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Real-time PCR analyses revealed expression of Lcn2 and its receptor by endothelial cells (EC) as well as a hypoxia-dependent up-regulation (rel. Lcn2 mRNA hypoxia vs. normoxia 1.6±0.2, P<0.05; rel. Lcn2-receptor mRNA hypoxia vs. normoxia 2.6±0.2, P<0.001). In the mouse aortic ring assay Lcn2-treatment resulted in a significant outgrowth of EC similar to VEGF. In the hind limb ischemia (HLI) model Lcn2 -/- mice showed an impressive phenotype. After induction of HLI we detected significantly more tissue defects compared to wild type (WT) mice. The ischemia-related lesions were more severe as determined by necrosis score (necrosis score Lcn2 -/- 1.8±0.2 vs. WT 0.7±0.2, n=5, P<0.01) and amputation rate was significantly higher. In ischemic hind limbs of Lcn2 -/- mice ERK1/2-phosphorylation was almost abrogated which might be an underlying mechanism. Transplantation of WT-bone marrow to irradiated Lcn2 -/- mice didn’t influence the outcome suggesting that observed effects are rather endothelium-dependent than influenced by an inflammatory response. Conclusion: Lcn2 might be a promising therapeutic factor for the treatment of ischemic vascular disorders.

scholarly journals Incorporation of platelet and leukocyte lipoxygenase metabolites by cultured vascular cells

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 373-378 ◽  
Author(s):  
AI Schafer ◽  
H Takayama ◽  
S Farrell ◽  
MA Jr Gimbrone
Keyword(s):  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Fatty Acid ◽  
Smooth Muscle Cells ◽  
Vascular Function ◽  
Muscle Cells ◽  
Arachidonic Acid Metabolism ◽  
Eicosatetraenoic Acid

Abstract When arachidonic acid metabolism is studied during platelet-endothelial interactions in vitro, the predominant cyclooxygenase end products of each cell type (thromboxane B2 and 6-keto-prostaglandin-F1 alpha, respectively) are essentially completely recovered in the cell-free supernatants of these reactions. In contrast, 50% of 12-hydroxy- 5,8,10,14-eicosatetraenoic acid (12-HETE), the major lipoxygenase metabolite from platelets, is released into the cell-free supernatant. In investigating the basis of this observation, we have found that platelet lipoxygenase metabolites were generated to the same extent during these coincubations but became rapidly incorporated into the endothelial cells. The endothelial cell-associated 12-HETE was present not only as free fatty acid, but was also incorporated into cellular phospholipids and triglycerides. When purified 3H-12-HETE, 3H-5-HETE (the major hydroxy acid lipoxygenase product of leukocytes), and 3H- arachidonic acid (the common precursor of these metabolites) were individually incubated with suspensions of cultured bovine aortic endothelial cells or smooth muscle cells, different patterns of intracellular lipid distribution were found. In endothelial cells, 12- HETE was incorporated equally into phospholipids and triglycerides, whereas 5-HETE was incorporated preferentially into triglycerides, and arachidonic acid was incorporated into phospholipids. In smooth muscle cells, both 12-HETE and 5-HETE showed more extensive incorporation into triglycerides. The rapid and characteristic incorporation and esterification of platelet and leukocyte monohydroxy fatty acid lipoxygenase products by endothelial and smooth muscle cells suggests a possible physiologic role for these processes in regulating vascular function.

Stabilin-1 and −2 constitute a novel family of fasciclin-like hyaluronan receptor homologues

2002 ◽  
Vol 362 (1) ◽  
pp. 155-164 ◽  
Author(s):  
Oliver POLITZ ◽  
Alexei GRATCHEV ◽  
Peter A. G. McCOURT ◽  
Kai SCHLEDZEWSKI ◽  
Pierre GUILLOT ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Function ◽  
Northern Blotting ◽  
Interleukin 4 ◽  
Alternatively Activated Macrophages ◽  
Cdna Sequences ◽  
Inflammatory Processes ◽  
Hyaluronan Receptor

MS-1, a high-molecular-mass protein expressed by non-continuous and angiogenic endothelial cells and by alternatively activated macrophages (Mφ2), and the hepatic sinusoidal endothelial hyaluronan clearance receptor are similar with respect to tissue distribution and biochemical characteristics. In the present study we purified these proteins by immuno- and hyaluronan-affinity chromatography respectively, sequenced tryptic peptides and generated full-length cDNA sequences in both mouse and human. The novel genes, i.e. stabilin-1 and stabilin-2, code for homologous transmembrane proteins featuring seven fasciclin-like adhesion domains, 18–20 epidermal-growth-factor domains, one X-link domain and three to six B-(X7)-B hyaluronan-binding motifs. Northern-blotting experiments revealed the presence of both stabilins in organs with predominant endothelial sinuses such as liver, spleen and lymph node: stabilin-1 mRNA was also detected in organs with predominant Mφ2 cells, such as placenta, and in interleukin-4/glucocorticoid-stimulated Mφ2 cells in vitro. A polyclonal antibody made against human recombinant stabilin-1 confirmed the expression of stabilin-1 protein in splenic sinus endothelial cells in vivo and in Mφ2 in vitro. On the basis of high similarity at the protein level and the unique domain composition, which differs from that of all other known fasciclin-like proteins and hyaluronan receptors, stabilin-1 and stabilin-2 define a novel family of fasciclin-like hyaluronan receptor homologues that might play a role in cell—cell and cell—matrix interactions in vascular function and inflammatory processes.

scholarly journals BIODEGRADABLE VASCULAR GRAFT MODIFIED BY RGD-PEPTIDES: EXPERIMENTAL RESEARCH

2019 ◽  
Vol 34 (2) ◽  
pp. 129-137
Author(s):  
E. O. Krivkina ◽  
V. N. Silnikov ◽  
A. V. Mironov ◽  
E. A. Velikanova ◽  
E. A. Senokosova ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Grafts ◽  
Small Diameter ◽  
Internal Surface ◽  
Mechanical Tests ◽  
Laboratory Animals ◽  
Rgd Peptides ◽  
Peptide Modification

Research goals. To study the effectiveness of RGD-peptide modification of the small-diameter biodegradable vascular grafts depending on the type of a linker and RGD configuration.Material and Methods. Tubular scaffolds with a diameter of 1.5 and 4.0 mm were produced by electrospinning from polyhydroxybutyrate/valerate (PHBV) and polycaprolactone (PCL). The PHBV/PCL grafts were modified with RGD peptides. In vitro experiments showed the degree of erythrocyte hemolysis and adhesion of the platelets and endothelial cells when in contact with a modified surface. The physico-mechanical properties and the structure of graft surface were studied before and after modification. The PHBV/PCL and PHBV/PCL/RGD vascular grafts were implanted into the abdominal aorta of rats for the periods of 1 and 3 months. Explant samples were studied using confocal microscopy and histological methods.Results. The results of physical and mechanical tests showed a significant decrease in the strength properties of the PHBV/PCL/RGD grafts relative to the unmodified analogs. A significant increase in platelet aggregation was found in the modified grafts. The level of adhesion of the endothelial cells on the modified surfaces was higher than that on the unmodified surfaces. Shortterm implantation of the grafts for 1 and 3 months showed that the modified grafts had higher patency and a less tendency to calcification compared with the unmodified grafts. Immunofluorescence study demonstrated the significant superiority of the modified vascular grafts in terms of stimulating the formation of a mature endothelial monolayer. A longer linker of 4,7,10-trioxa-1,13-tridecane diamine was found to increase the bioavailability of RGD peptides; the use of RGDK and c[RGDFK] for surface modification of the grafts stimulated early endothelialization of the internal surface of the implants and reduced the prosthetic wall calcification tendency, which together increased the patency of the implanted grafts.Conclusion. In short-term implantation of biodegradable vascular grafts modified with RGD peptides, the grafts with RGDK and c[RGDFK], attached to the surface of the prostheses through the 4,7,10-triox-1,13-tridecane diamine linker, showed the best results in terms of endothelial adhesion and maintenance of the viability of the endothelial cells in vitro and endothelialization in vivo; these grafts had high patency after implantation into the bloodstream of small laboratory animals and a less tendency to calcification.

NO synthesis is involved in structural and functional effects of ACE inhibitors in injured arteries

1996 ◽  
Vol 270 (1) ◽  
pp. H298-H305 ◽  
Author(s):  
E. Van Belle ◽  
B. Vallet ◽  
J. L. Auffray ◽  
C. Bauters ◽  
M. Hamon ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ace Inhibitors ◽  
Intimal Hyperplasia ◽  
Vascular Function ◽  
Ace Inhibitor ◽  
White Male ◽  
Rabbit Model ◽  
Balloon Injury

Angiotensin-converting enzyme (ACE) inhibitors reduce intimal hyperplasia after balloon injury. A role for nitric oxide (NO) has been suggested in this effect. Because recent data suggest that NO may modulate some features of endothelial cells and because endothelial cells are involved in the control of intimal hyperplasia, we investigated the role of NO synthesis in the effect of an ACE inhibitor, perindopril, on neoendothelial dysfunction and intimal hyperplasia in a rabbit model of unilateral iliac balloon injury. New Zealand White male rabbits received placebo, perindopril, or cotreatment with perindopril and NG-nitro-L-arginine methyl ester (L-NAME) and were evaluated 4 wk after the injury. Fifteen rabbits (5 in each group) were used to assess in vitro vasoreactivity and twenty-four (8 in each group) for morphometric analysis. In injured vessels, neoendothelium-dependent relaxation in ACE inhibitor-treated animals was improved compared with placebo (P < 0.05) and restored to the level of noninjured vessels (NS). The improvement observed with ACE inhibitor was abolished by cotreatment with L-NAME (P < 0.05). In the same vessels, no effect was observed on neoendothelium-independent vasoreactivity. The improved neoendothelial dysfunction with ACE inhibitor was associated with a 66% reduction in intimal thickening (P < 0.01). The effect was also reversed by cotreatment with L-NAME (P < 0.01). In noninjured vessels, treatment did not alter vasoreactivity or morphology of the vessel wall. These results suggest that NO synthesis may play a key role in the improvement of vascular function seen with ACE inhibitor in balloon-injured vessels.

VEGF-VEGF Receptor 1 (Flt-1) Interactions Significantly Modulate Endothelial Progenitor Cell (EPC) Migration but Have Only Minor Effects on the Migration of Differentiated Endothelial Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3229-3229
Author(s):  
Bin Li ◽  
Amylynn A. Teleron ◽  
Charles Lin ◽  
Pampee P. Young
Keyword(s):  
Wound Healing ◽  
Endothelial Cells ◽  
Blood Vessel ◽  
Vegf Receptor ◽  
Blocking Antibody ◽  
Blood Vessel Formation ◽  
Migration Assay ◽  
Vessel Formation ◽  
Cellular Expression

Abstract There is a growing body of data demonstrating that vasculogenesis, whereby bone marrow -derived circulating progenitor cells (EPCs) home to sites of neovascularization, results in significant contribution to blood vessel formation during tumor growth, ischemic injury and wound healing. Vascular Endothelial Growth Factor (VEGF) has recently been shown to augment vasculogenesis. In the current study, we examined if VEGF/VEGF Receptor (VEGFR) interactions are important for EPC recruitment. Both VEGFR1 (flt-1) and VEGFR2 (flk-1) are strongly expressed, as detected by immunofluorescent and FACS analysis, on EPCs obtained by ex vivo expansion of human peripheral blood. In a modified Boyden chamber migration assay, EPCs showed dose dependent migration to VEGF. To examine receptor specificity, EPCs were preincubated with receptor blocking anti-VEGFR1 or -VEGFR2 prior to the migration assay. Level of inhibition by VEGFR1 blocking antibody was commensurate with blocking VEGFR2. Furthermore, migration in response to a VEGFR1-specific agonist, PlGF, was comparable to that induced by VEGF and was completely ablated by preincubation with VEGFR1 blocking antibody. By contrast, differentiated endothelial cells had diminished migration in response to PlGF as compared to VEGF. Furthermore, blocking VEGFR1 only mildly disrupted VEGF-induced migration of differentiated endothelial cells in vitro. Hence, unlike differentiated endothelial cells, EPC migration in vitro was mediated by both VEGF receptors. By quantitative RT-PCR, we examined the level of VEGFR1 and VEGFR2 mRNA transcripts in EPCs versus differentiated endothelial cells. VEGFR1 transcripts in EPCs were expressed 3-fold higher than in differentiated endothelial cells. VEGFR2 and neuropilin transcript levels in EPCs, however, were lower than in differentiated endothelial cells. These results suggest that VEGF/VEGFR1 interactions are important in EPC migration in vitro. We have subcloned VEGFR1 cDNA into a retrovirus vector and have shown by western blot that we can direct increased cellular expression of VEGFR1. In further experiments, we will examine the role of VEGFR1 in human EPC recruitment using murine xenotransplant models of hindlimb ischemia and wound healing. These studies will provide valuable insight towards developing EPCs as cellular therapy to augment blood vessel formation.

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