Biomedical subjects

Annette Schmidt

Publications and source records attributed to Annette Schmidt.

At least 19 recordsLinked to original sources

PubMed2006

Pro-inflammatory cytokines in elective flap surgery.

BACKGROUND: Surgical trauma releases inflammatory mediators such as pro-inflammatory cytokines. In this prospective, controlled, randomized trial we investigated the release of pro-inflammatory cytokines and monocyte/macrophage activation in patients scheduled for breast reconstruction after mastectomy. Patients were allocated to one of three surgical procedures, differing in complexity and in the need for implants used for reconstruction. METHODS: Thirty mastectomized women underwent delayed breast reconstruction with the lateral thoracodorsal flap (LTD), the latissimus dorsi flap (LD), or the pedicled transverse rectus abdominis muscle flap (TRAM). Blood samples for TNF, IL-6, IL-8, neopterin, C-reactive protein (CRP), and leukocyte determination were drawn pre-operatively, 24 h, and 2 weeks post-operatively. RESULTS: All groups had significantly elevated IL-6 levels 24 h after surgery. The levels were significantly higher in the TRAM group compared to the LTD and LD groups. IL-8 levels were increased in all groups 2 weeks after surgery (P < 0.05), the LTD (83 pg/mL) and LD (84 pg/mL) group having higher mean IL-8 levels than the TRAM patients (48 pg/mL) (ns). TNF and leukocyte counts were within the normal range. CRP levels were elevated in all groups one day after surgery (P < 0.05). CONCLUSION: Flap procedures for breast reconstruction stimulate the pro-inflammatory response. IL-6 levels were highest in patients with TRAM operations, being the most extensive procedure studied, whereas the highest IL-8 levels were seen in women with a saline filled silicone implant suggesting immunomodulation by foreign material. Although all three investigated procedures are major operations in the field of plastic surgery, according to the inflammatory response to trauma they should be regarded as minor procedures.

Adult↗

PubMed2006

Acute BDNF and cortisol response to low intensity exercise and following ramp incremental exercise to exhaustion in humans.

The effect of short-term aerobic exercise and a following ramp incremental cycle ergometry to exhaustion on the acute response of the serum concentrations of brain derived neurotrophic factor (BDNF) and cortisol (COR) was examined in 8 healthy male athletes. Venous and capillary blood samples were drawn at rest, immediately after a 10 min warm-up period with aerobic exercise and after a ramp test to exhaustion, as well as 3, 6, 10 and 15 min post exercise. Capillary blood lactate (LA) concentration and blood gases as well as serum BDNF and COR concentrations did not change during the warm-up period. LA was increased (p<0.05) at the end of the ramp test and during recovery period while bicarbonate concentration, carbon dioxide pressure, pH and base excess were decreased (p<0.05) during this period. Serum BDNF was increased at the point of exhaustion (p<0.05) while no significant differences were found between values at rest and those during recovery period. At 10 and 15 min post incremental exercise, COR concentrations were increased (p<0.05) compared to rest. The present study is the first to demonstrate in humans that in contrast to short duration aerobic exercise immediately after a following short duration high-intensity exercise to exhaustion, there is a transient augmentation of serum BDNF concentration. Short-term response of serum BDNF and COR concentrations differs as BDNF returns to baseline level faster than COR.

Adult↗

PubMed2006

Mesenchymal stem cells transmigrate over the endothelial barrier.

Mesenchymal stem cells (MSCs) seem to be a useful tool for cellular therapy in injured tissues, e.g. myocardial infarction or cardiomyopathies resulting in heart failure. For therapeutic approaches it is crucial that MSCs cross the endothelial barrier especially in intravascular or rather intracoronary application. Until today little is known about MSCs transmigrating across the endothelium. We performed co-culture experiments of MSCs on an endothelial monolayer to analyse direct interactions. An increasing flattened morphology of the MSCs was followed by a total integration into the monolayer after 2h. We repeated these experiments in isolated heart perfusions with gold-labelled MSCs. Using electron microscopy we detected MSCs exhibited direct cell-cell contacts. Tight junctions between the endothelial cells became abolished resulting in a distinct split between the cells. MSCs developed tight cell-cell contacts and became integrated into the endothelial wall of the capillary vessel. Finally, using confocal laser scanning microscopy, we assessed the ability of the MSCs to fully pass the endothelial barrier. Within the first 30 min, 30+/-8% of MSCs transmigrated, increasing to about half at 60 min (50+/-8%), whereas after 120 min the rate remained nearly unchanged (53+/-10%). This work demonstrates the capability of MSCs for transendothelial migration. Moreover we showed that the vast majority of MSCs migrated within 30 min, an important finding for the exposure times in clinical settings.

Animals↗

PubMed2006

Volatilisation of metals and metalloids by the microbial population of an alluvial soil.

In order to assess the microbial contribution to the volatilisation of metal(loid)s by methylation and hydridisation in the environment, we focused on soils of different origin. Here, we describe the biogenic production of volatile metal(loid) species of an alluvial soil with rather low metal(loid) contamination. The production of volatile metal(loid) compounds was monitored in soil suspensions kept under anaerobic conditions over an incubation time of 3 months. In the headspace of the samples, we detected mainly hydrids and methylated derivatives of a broad variety of elements such as arsenic, antimony, bismuth, selenium, tellurium, mercury, tin and lead, with the volatile products of arsenic, antimony and selenium representing the highest portions. Classical cultivation-dependent procedures resulted in the isolation of a strictly anaerobic Gram-positive strain (ASI-1), which shows a high versatility in transforming metal(loid) ions to volatile derivatives. Strain ASI-1 is affiliated to the species Clostridium glycolicum due to its high 16S rDNA sequence similarity with members of that species. As shown by fluorescence in situ hybridisation, strain ASI-1 amounts to approximately 2% of the total microbial flora of the alluvial soil. Since the spectrum of volatile metal(loid) compounds produced by this strain is very similar to that obtained by the whole population regarding both the broad variety of metal(loid)s converted and the preference for volatilising arsenic, antimony and selenium, we suggest that this strain may represent a dominant member of the metal(loid) volatilisating population in this habitat.

Anaerobiosis↗

PubMed2006

Human bone marrow stroma cells display certain neural characteristics and integrate in the subventricular compartment after injection into the liquor system.

Because the neural differentiation capacity of bone marrow stromal cells (BMSCs) is still a matter of controversial debate, we performed a thorough investigation into the differentiation capacity of human BMSCs and examined their therapeutic potency. BMSCs were isolated from the femur and kept in cell cultures with various cultivation protocols being applied. In standard culture conditions using a fetal calf serum-enriched medium, while not exhibiting a neural phenotype, the majority of cells expressed a variety of neuronal marker proteins as well as the astrocyte marker GFAP. Only a minority of stem cells expressed nestin, a marker for neural precursor cells. Cultivation in serum-free medium supplemented with specific growth factors resulted in a markedly higher percentage of nestin-positive cells. To establish the therapeutic potency of bone marrow-derived cells, the synthesis of neurotrophic factors such as NGF, BDNF and GDNF was analyzed under non-stimulating standard culture conditions as well as after a neural selection procedure. The therapeutic potency of BMSCs was further examined with regard to their migratory potential in vitro and after transplantation in vivo. After stereotactic engraftment into the lateral ventricle of adult rats, mesenchymal stem cells were seen to adhere to the ependymocytes and cells of the choroids plexus. Afterwards grafted cells passed through the ependymal barrier, locating in the subventricular space. Their BMSCs took up a close host graft interaction without any degenerative influence on the host cells. Furthermore, there was morphological as well as immunohistochemical evidence for a transdifferentiation within the host tissue. In addition, BMSCs could be efficiently transduced using a third-generation adenoviral vector, indicating their potential feasibility for a gene-therapeutic option.

Adenoviridae↗

PubMed2006

Endostatin influences endothelial morphology via the activated ERK1/2-kinase endothelial morphology and signal transduction.

Endostatin, the proteolytic fragment of collagen XVIII, is known to be a potent inhibitor of angiogenesis. However, to date, only limited knowledge exists with regard to the effects of endostatin on vessel morphology and the underlying signaling pathway. The aim of the present work was therefore to determine the impact of endostatin and its collagen XV analogue restin on vessel development during wound healing and embryonic angio- and vasculogenesis. Time lapse experiments and electron microscopy demonstrate similar morphological changes evoked by endostatin and the ERK1/2-kinase inhibitor PD98059. Furthermore, we show that ERK1/2 phosphorylation, a crucial signaling event in vascular morphogenesis, is regulated by endostatin via the protein phosphatase 2A PP2A. These findings provide new insight into a key signaling pathway of vascular remodeling evoked by a matrix-derived factor.

Angiogenesis Inhibitors↗

PubMed2006

The antiatherogenic and antiinflammatory effect of HDL-associated lysosphingolipids operates via Akt -->NF-kappaB signalling pathways in human vascular endothelial cells.

Adhesion of mononuclear cells to the vascular endothelium and their subsequent transmigration into the arterial wall represent key events in the pathogenesis of arteriosclerosis. In previous studies we have shown that high density lipoproteins (HDL) and the HDL-associated sphingosylphosphorylcholine (SPC) have the ability to suppress the TNF-alpha-induced expression of endothelial cell E-selectin. However, the current understanding of the mechanism by which HDL reduces the expression of E-selectin is still incomplete. In the present study we show that interaction of the HDL-associated sphingosylphosphorylcholine and sphingosylgalactosyl-3-sulfate (lysosulfatide, LSF) with the G-protein-coupled EDG receptor initiates a signalling cascade that activates the protein kinase Akt and reduces the E-selectin, ICAM-1 and VCAM-1 expression on protein and mRNA level. This signalling cascade is consistently associated with a reduced translocation of TNF-alpha-activated NF-kappaB into the cell nucleus. The suppressor effect of SPC and LSF is completely reverted by inhibition of the phosphatidylinositol- 3-kinase/Akt pathway. We conclude that the antiatherogenic/antiinflammatory effect of lysosphingolipids depends on a competitive interaction of EDG receptor-induced inhibition and TNF-alpha-initiated stimulation of NF-kappaB translocation into the cell nucleus thereby preventing or stimulating inflammatory events in atherogenesis.

Atherosclerosis↗

PubMed2006

Basic fibroblast growth factor controls migration in human mesenchymal stem cells.

Little is known about the migration of mesenchymal stem cells (MSCs). Some therapeutic approaches had demonstrated that MSCs were able to regenerate injured tissues when applied from different sites of application. This implies that MSCs are not only able to migrate but also that the direction of migration is controlled. Factors that are involved in the control of the migration of MSCs are widely unknown. The migratory ability of isolated MSCs was tested in different conditions. The migratory capability was examined using Boyden chamber assay in the presence or absence of basic fibroblast growth factor (bFGF), erythropoietin, interleukin-6, stromal cell-derived factor-beta, and vascular endothelial growth factor. bFGF in particular was able to increase the migratory activity of MSCs through activation of the Akt/protein kinase B (PKB) pathway. The results were supported by analyzing the orientation of the cytoskeleton. In the presence of a bFGF gradient, the actin filaments developed a parallelized pattern that was strongly related to the gradient. Surprisingly, the influence of bFGF was not only an attraction but also routing of MSCs. The bFGF gradient experiment showed that low concentrations of bFGF lead to an attraction of the cells, whereas higher concentrations resulted in repulsion. This ambivalent effect of bFGF provides the possibility to a purposeful routing of MSCs.

Actins↗

PubMed2005

Effect of adjuvant on reactogenicity and long-term immunogenicity of the malaria Vaccine ICC-1132 in macaques.

ICC-1132 is a malaria vaccine candidate based on a modified hepatitis B virus core particle (HBc) bearing putative protective epitopes from the circumsporozoite protein (CS) of Plasmodium falciparum. While the epitope carrier itself is immunogenic, its potency can be increased by formulation with adjuvants. As a prelude to Phase I clinical trials, rhesus macaques were immunised twice with GMP grade ICC--1132 in saline or formulated with the adjuvants Alhydrogel (Alhydrogel) or Montanide((R)) ISA 720 (Montanide). Both adjuvant formulations gave significant humoral responses after the first injection, with titres increasing further after the second dose. The Montanide formulation was the most immunogenic, but undesirable reactogenicity in the form of sterile abscesses was associated with higher dosage levels of ICC--1132. These side effects could be avoided with lower antigen load, or by formulation of the second dose in Alhydrogel. Such measures also reduced peak titres and longevity of antibodies against CS, demonstrating the delicate balance between immunogenicity and reactogenicity of new vaccine formulations.

Abscess↗

PubMed2005

Plasmin- and thrombin-accelerated shedding of syndecan-4 ectodomain generates cleavage sites at Lys(114)-Arg(115) and Lys(129)-Val(130) bonds.

Syndecans are transmembranous heparan sulfate proteoglycans abundant in the surface of all adherent mammalian cells and involved in vital cellular functions. In this study, we found syndecan-1, -2, -3, and -4 to be constitutively expressed by human umbilical vein endothelial cells. The exposure of the ectodomains of syndecan-1 and -4 to the cell surface and their constitutive shedding into the extracellular compartment was measured by immunoassays. In the presence of plasmin and thrombin, shedding was accelerated and monitored by detection and identification of (35)S-labeled proteoglycans. To elucidate the cleavage site of the syndecan ectodomains, we used a cell-free in vitro system with enzyme and substrate as the only reactants. For this purpose, we constructed recombinant fusion proteins of the syndecan-1 and -4 ectodomain together with maltose-binding protein and enhanced yellow fluorescent protein as reporter proteins attached to the N and C termini via oligopeptide linkers. After protease treatment of the fusion proteins, the electrophoretically resolved split products were sequenced and cleavage sites of the ectodomain were identified. Plasmin generated cleavage sites at Lys(114) downward arrowArg(115) and Lys(129) downward arrowVal(130) in the ectodomain of syndecan-4. In thrombin proteolysates of the syndecan-4 ectodomain, the cleavage site Lys(114) downward arrowArg(115) was also identified. The cleavage sites for plasmin and thrombin within the syndecan-4 ectodomain were not present in the syndecan-1 ectodomain. Cleavage of the syndecan-1 fusion protein by thrombin occurred only at a control cleavage site (Arg downward arrowGly) introduced into the linker region connecting the ectodomain with the enhanced yellow fluorescent protein. Because both plasmin and thrombin are involved in thrombogenic and thrombolytic processes in the course of the pathogenesis of arteriosclerosis, the detachment of heparan sulfate-bearing ectodomains could be relevant for the development of arteriosclerotic plaques and recruitment of mononuclear blood cells to the plaque.

Amino Acid Sequence↗

PubMed2005

Role of erythropoietin for angiogenesis and vasculogenesis: from embryonic development through adulthood.

Erythropoietin (EPO), a stimulator of erythropoiesis, was previously shown to stimulate angiogenesis and proliferation of endothelial cells. Here, we investigated and compared the influence of EPO on cell number, proliferation, apoptosis, migration, and differentiation of endothelial cells in intact mouse embryoid bodies (EB), isolated endothelial cells from EB (EBEC), and adult human endothelial progenitor cells (hEPC). EB were treated with EPO (0.5 U/ml) immediately after plating was completed (day 5+0) or 3 days later. EPO treatment was continued until days 5+3 or 5+6. Cultured EBEC were treated 3 days after being plated, and primary hEPC from young healthy adults were treated 5 days after being plated with EPO for 48 h. Immunohistochemistry was performed with anti-PECAM (CD31), anti-Ki67, anti-CD34, anti-CD133, anti-EphB4, and anti-ephrinB2 antibodies. In all, mouse EB and EBEC and hEPC, EPO-treatment resulted in increased number of endothelial cells, increased proliferation, decreased apoptosis, and enhanced migration. In EB, this EPO effect was most pronounced when treatment was begun early (day 5+0) and was accompanied by an enhanced endothelial tube formation. In EBEC and hEPC, EPO shifted the phenotypic differentiation toward an increased ratio of EphB4-positive cells, i.e., toward a venous phenotype. These results are consistent with an important role of EPO for the number, proliferation, apoptosis, function, and phenotypical development of immature endothelial cells, which persists from early development through adulthood. They provide additional and further evidence for a strong interrelation between hematopoiesis and vasculogenesis/angiogenesis (sharing the same pathways), which may be important in many physiological and pathophysiological conditions.

AC133 Antigen↗

PubMed2005

Heterozygous deficiency of manganese superoxide dismutase results in severe lipid peroxidation and spontaneous apoptosis in murine myocardium in vivo.

To circumvent the early lethality of manganese superoxide dismutase (SOD2)-deficient mice, we have used a skin-specific strategy with introduction of loxP sites flanking exon 3 of the SOD2 gene. To our surprise, when breeding a female keratin 14 Cre transgenic mouse to a SOD2 "floxed" male mouse, due to keratin 14 promoter-driven Cre expression in the oocytes, all offspring were heterozygous for SOD2. In sharp contrast to initial publications on SOD2(+/-) mice, the herein reported mice on a mixed genetic background (C57BL/6 x 129/Ola) in their heterozygous state (SOD(+/-)) revealed distinct ultrastructural damage of the myocard, with swelling and disruption of mitochondria and accumulation of lipid droplets, increased nitrotyrosine formation, and lipid peroxidation as well as activation of apoptosis signaling pathways in the heart in vivo. Strikingly, and so far unreported, we found a substantial decrease in the activity of the cytosolic copper, zinc superoxide dismutase (SOD1) in the heart tissue of SOD2(+/-) mice, suggesting that the breakdown of mitochondrial membranes in the heart of SOD2(+/-) mice results in the enhanced release of superoxide anion radicals or derivatives thereof with subsequent inactivation of cytosolic SOD1. This model may be particularly suited to long-term studies on age-related heart failure as well as other age-related diseases and the polygenic base of tissue-specific responses to oxidative injury.

Animals↗

PubMed2005

Safety, immunogenicity and efficacy of a pre-erythrocytic malaria candidate vaccine, ICC-1132 formulated in Seppic ISA 720.

ICC-1132, a recombinant virus-like particle comprising of a modified hepatitis B core protein with a B cell (NANP) and two T cell epitopes of Plasmodium falciparum circumsporozoite protein (CSP), was administered i.m. as a single 50 microg dose in Seppic ISA 720 to 11 volunteers. Local reactogenicity and systemic side effects were acceptable with the predominant finding being mild pain at the injection site. This regimen induced anti-NANP antibodies in 10/11 and modest T cell responses. There was no evidence of protection from experimental challenge with P. falciparum sporozoites. Other formulations and/or multi-dose regimens will be required to enhance the immunogenicity and efficacy of ICC-1132.

Adult↗

PubMed2005

Phospho-eNOS Ser-114 in human mesenchymal stem cells: constitutive phosphorylation, nuclear localization and upregulation during mitosis.

Activity of endothelial nitric oxide synthase (eNOS) is modulated by protein-protein interaction and phosphorylation at specific serine or threonine residues. Using immunofluorescence analysis we show here that proliferating mesenchymal stem cells (MSCs) derived from human bone marrow exhibit cytosolic and pronounced nuclear localization of eNOS. Examination of phosphorylated eNOS subspecies revealed that eNOS phosphorylated at Ser-114 is heavily enriched in the nucleus, whereas eNOS phosphorylated at Ser-1177 is localized at filamentous structures in the cytosol that are abundant in the perinuclear region. Phosphorylation of eNOS at Ser-114 but not at Ser-1177 was strongly increased in cells shortly before mitosis and decreased to normal level after completed cell division. Double immunofluorescence analysis revealed that subcellular localization of 8-hydroxyguanosine immunoreactivity was overlapping with eNOS phosphorylated at Ser-114 in human MSCs providing evidence that phosphorylation at this residue is linked to the generation of superoxide anions. As expected there was only a weak colocalization between eNOS phosphorylated at Ser-1177 and caveolin-1. Different from many other cell systems, human MSCs accumulate eNOS in the nucleus without an acute stimulus. eNOS constitutively phosphorylated at distinct amino acid residues is targeted to different subcellular compartments pointing to an important role of specific phosphorylation events in the life cycle of proliferating human MSCs.

Active Transport, Cell Nucleus↗

PubMed2005

Orthotopic liver transplantation in a malignant hyperthermia susceptible patient.

We present a patient with hepatitis C and D and hepatocellular carcinoma who underwent preoperative evaluation for orthotopic liver transplantation. In his past medical history, he reported a life-threatening event during tonsillectomy in 1975. Intubation was impossible due to extreme jaw muscle tension, followed by excessive elevation in body temperature, tachycardia, and coma for a few days. We evaluated him for malignant hyperthermia, according to the European Malignant Hyperthermia Group Protocol, and found him highly positive in both the halothane and caffeine test, respectively. Three months later, we performed an orthotopic liver transplantation. During retransplantation 4 years later, due to ischemic-type biliary lesions, he suffered massive intraoperative bleeding. Blood products, as well as coagulation factors and aprotinin, were well tolerated. Anesthesia was performed in a trigger-free total intravenous technique without dantrolene prophylaxis, but dantrolene was readily available in sufficient quantities in the operating room. The patient did not encounter a malignant hyperthermia crisis in either perioperative period.

Adult↗

PubMed2005

Differential endostatin binding to bladder, prostate and kidney tumour vessels.

OBJECTIVES: To define the anti-angiogenic mechanism and causes of the heterogeneous influence of endostatin, one of a group of matrix-derived inhibitors of tumour angiogenesis of increasing significance in tumour treatment, on various tissue types. MATERIALS AND METHODS: Variations in the binding behaviour of endostatin with vessels were assessed in different tumours (bladder, prostate and kidney) and compared with benign tissue vessels. Biotinylated endostatin was used and detected using extravidin CY3 and extravidin-gold immunolabelling. RESULTS: There were significant differences in the number of vessels showing endostatin binding among benign and malignant bladder, prostate and kidney tissues. While there was distinct endostatin binding on a mean (sd) of 94.2 (3.0)% bladder and 73.8 (19.5)% prostate tumour vessels, there was less binding, at 11.32 (3.9)%, on kidney tumour vessels. There was less binding to vessels of benign bladder, prostate and kidney tissue, at 2.0 (1.5), 1.7 (1.7) and 1.5 (1.7)%, respectively. At the ultrastructural level, different binding sites were detected both inside and outside the endothelial cells. CONCLUSION: Endostatin binds more to all tumour tissues than to benign tissue, but the degree of binding in malignant kidney tissue was significantly less than that in malignant prostate and bladder tissues. These divergent vascular endostatin-binding patterns could be responsible for a tumour type-dependent anti-angiogenic effect attributable to endostatin. Such selective behaviour would have therapeutic consequences for future anti-angiogenic therapy, in which different kinds of tumours could be further classified into those responding to endostatin or not.

Aged↗

PubMed2005

Safety and enhanced immunogenicity of a hepatitis B core particle Plasmodium falciparum malaria vaccine formulated in adjuvant Montanide ISA 720 in a phase I trial.

Highly purified subunit vaccines require potent adjuvants in order to elicit optimal immune responses. In a previous phase I trial, an alum formulation of ICC-1132, a malaria vaccine candidate comprising hepatitis B core (HBc) virus-like particle containing Plasmodium falciparum circumsporozoite (CS) protein epitopes, was shown to elicit Plasmodium falciparum-specific antibody and cellular responses. The present study was designed as a single-blind, escalating-dose phase I trial to evaluate the safety and immunogenicity of single intramuscular doses of ICC-1132 formulated in the more potent water-in-oil adjuvant Montanide ISA 720 (ICC-1132/ISA 720). The vaccine was safe and well tolerated, with transient injection site pain as the most frequent complaint. All vaccinees that received either 20 mug or 50 mug of ICC-1132/ISA 720 developed antiimmunogen and anti-HBc antibodies. The majority of volunteers in these two groups developed sporozoite-specific antibodies, predominantly of opsonizing immunoglobulin G subtypes. Peak titers and persistence of parasite-specific antibody following a single injection of the ISA 720 formulated vaccine were comparable to those obtained following two to three immunizations with alum-adsorbed ICC-1132. Peripheral blood mononuclear cells of ICC-1132/ISA 720 vaccinees proliferated and released cytokines (interleukin 2 and gamma interferon) when stimulated with recombinant P. falciparum CS protein, and CS-specific CD4(+) T-cell lines were established from volunteers with high levels of antibodies to the repeat region. The promising results obtained with a single dose of ICC-1132 formulated in Montanide ISA 720 encourage further clinical development of this malaria vaccine candidate.

Adjuvants, Immunologic↗

PubMed2004

Opposite effects of endostatin on different endothelial cells.

Endostatin was described as an anti-angiogenic factor. Therefore endostatin looked to be a new way in anti-angiogenic treatment of cancer. Unfortunately, up to now no objective response were seen in clinical trials using endostatin. We compared two different endothelial cell types. Human umbilical vein endothelial cells (HUVEC) and endothelial cells derived from differentiated embryonic stem cells (eESC) were tested in view of endostatin induced proliferation, apoptosis, migration and endostatin binding. Both endothelial cell types had shown an opposite response to endostatin for all observed parameters in dependency of the used concentration. The quantity of HUVEC cells was slightly reduced to 84 +/- 8% by treating with 50 ng/ml endostatin whereas the eESC's showed a significant increase up to 142 +/- 12% under same conditions (p = 0.01). The observation that endostatin is able to evoke non-uniform response for proliferation, cell mount and migration of endothelial cells, with different endostatin binding characteristic, leads to the assumption that endostatin effect is strongly dependent from endothelial cell type. Furthermore the cell biological response at lower concentration on angiogenic eESC gives evidence for an angiogenic modulatory rather than a predicted anti-angiogenic role of endostatin.

Angiogenesis Inhibitors↗