Search results for "physiologic"
showing 10 items of 2593 documents
In vitro and in vivo arterial differentiation of human multipotent adult progenitor cells
2006
Many stem cell types have been shown to differentiate into endothelial cells (ECs); however, their specification to arterial or venous endothelium remains unexplored. We tested whether a specific arterial or venous EC fate could be induced in human multipotent adult progenitor cells (hMAPCs) and AC133(+) cells (hAC133(+)). In vitro, in the presence of VEGF(165), hAC133(+) cells only adopted a venous and microvascular EC phenotype, while hMAPCs differentiated into both arterial and venous ECs, possibly because hMAPCs expressed significantly more sonic hedgehog (Shh) and its receptors as well as Notch 1 and 3 receptors and some of their ligands. Accordingly, blocking either of those pathways …
Extracellular HSP27 mediates angiogenesis through Toll-like receptor 3.
2013
The heat-shock protein 27 (HSP27) is up-regulated in tumor cells and released in their microenvironment. Here, we show that extracellular HSP27 has a proangiogenic effect evidenced on chick chorioallantoic membrane. To explore this effect, we test the recombinant human protein (rhHSP27) at physiopathological doses (0.1-10 μg/ml) onto human microvascular endothelial cells (HMECs) grown as monolayers or spheroids. When added onto HMECs, rhHSP27 dose-dependently accelerates cell migration (with a peak at 5 μg/ml) and favors spheroid sprouting within 12-24 h. rhHSP27 increases VEGF gene transcription and promotes secretion of VEGF-activating VEGF receptor type 2. Increased VEGF transcription is…
Integrin-dependent and -independent functions of astrocytic fibronectin in retinal angiogenesis
2011
Fibronectin (FN) is a major component of the extracellular matrix and functions in cell adhesion, cell spreading and cell migration. In the retina, FN is transiently expressed and assembled on astrocytes (ACs), which guide sprouting tip cells and deposit a provisional matrix for sprouting angiogenesis. The precise function of FN in retinal angiogenesis is largely unknown. Using genetic tools, we show that astrocytes are the major source of cellular FN during angiogenesis in the mouse retina. Deletion of astrocytic FN reduces radial endothelial migration during vascular plexus formation in a gene dose-dependent manner. This effect correlates with reduced VEGF receptor 2 and PI3K/AKT signalli…
The impact of intercellular communication for the generation of complex multicellular prevascularized tissue equivalents
2019
In reconstructive surgery the use of prevascularized soft tissue equivalents is a promising approach for wound coverage of defects after tumor resection or trauma. However, in previous studies to generate soft tissue equivalents on collagen membranes, microcapillaries were restricted to superficial areas. In this study, to understand which factors were involved in the formation of these microcapillaries, the levels of the angiogenic factors vascular endothelial growth factor (VEGF), Interleukin-8 (IL-8), and basic fibroblast growth factor (bFGF) in the supernatants of the tissue equivalents were examined at various time points and conditions. Additionally, the influence of these factors on …
Scaffold vascularization in vivo driven by primary human osteoblasts in concert with host inflammatory cells.
2011
Successful cell-based tissue engineering requires a rapid and thorough vascularization in order to ensure long-term implant survival and tissue integration. The vascularization of a scaffold is a complex process, and is modulated by the presence of transplanted cells, exogenous and endogenous signaling proteins, and the host tissue reaction, among other influencing factors. This paper presents evidence for the significance of pre-seeded osteoblasts for the in vivo vascularization of a biodegradable scaffold. Human osteoblasts, cultured on silk fibroin micronets in vitro, migrated throughout the interconnected pores of the scaffold and produced extensive bone matrix. When these constructs we…
The impact of the receptor binding profiles of the vascular endothelial growth factors on their angiogenic features
2013
Abstract Background Vascular endothelial growth factors (VEGFs) are potential therapeutic agents for treatment of ischemic diseases. Their angiogenic effects are mainly mediated through VEGF receptor 2 (VEGFR2). Methods Receptor binding, signaling, and biological efficacy of several VEGFR2 ligands were compared to determine their characteristics regarding angiogenic activity and vascular permeability. Results Tested VEGFR2 ligands induced receptor tyrosine phosphorylation with different efficacy depending on their binding affinities. However, the tyrosine phosphorylation pattern and the activation of the major downstream signaling pathways were comparable. The maximal angiogenic effect stim…
Comparative study assessing effects of sonic hedgehog and VEGF in a human co-culture model for bone vascularisation strategies.
2011
The morphogen sonic hedgehog (Shh) seems to mediate adult repair processes in bone regeneration and vascularisation. In this study we investigated the effects of Shh on co-cultures consisting of human primary osteoblasts and outgrowth endothelial cells in terms of angiogenic activation and vessel maturation in comparison to the treatment with the commonly used proangiogenic factor, VEGF. Both, stimulation with VEGF or Shh, leads to an increase in the formation of microvessel-like structures compared to untreated controls. In contrast to VEGF, proangiogenic effects by Shh could already be observed after 24 h of treatment. Nevertheless, after 14 days the angiogenic activity of OEC was compara…
Capillary enlargement, not sprouting angiogenesis, determines beneficial therapeutic effects and side effects of angiogenic gene therapy.
2010
Aims Currently, it is still unclear which mechanisms drive metabolic benefits after angiogenic gene therapy. The side-effect profile of efficient angiogenic gene therapy is also currently incompletely understood. In this study, the effects of increasing doses of adenoviral (Ad) vascular endothelial growth factor-A (VEGF-A) were evaluated on vascular growth, metabolic benefits, and systemic side effects. Methods and results Adenoviral vascular endothelial growth factor-A or AdLacZ control was injected intramuscularly (109–1011 vp/mL) or intra-arterially (5 × 1011 vp/mL) into rabbit ( n = 102) hindlimb muscles and examined 6 or 14 days later. Blood flow, tissue oedema, metabolic benefits, and…
Sonic hedgehog promotes angiogenesis and osteogenesis in a coculture system consisting of primary osteoblasts and outgrowth endothelial cells.
2009
A number of previous studies documented the angiogenic potential of outgrowth endothelial cells in vitro and in vivo and provided evidence that therapeutic success could depend on coculture or coimplantation strategies. Thus, deeper insight into the molecular mechanisms underlying this pro-angiogenic effect of cocultures might provide new translational options for tissue engineering and regenerative medicine. One promising signaling pathway in bone repair involved in neoangiogenesis and bone formation is the sonic hedgehog (Shh) pathway. In this article, we focus on the effect of Shh on the formation of microvessel-like structures and osteoblastic differentiation in cocultures of primary os…
Priming with a combination of proangiogenic growth factors improves wound healing in normoglycemic mice
2011
Growth factors and/or angiogenic factors are supposed to improve wound healing. The aim of our study was to evaluate the effects of subcutaneous pretreatment with combinatory proangiogenic factors on wound closure, mechan - ical properties, vessel density and morphology. Twenty-eight Balb/c mice were divided equally into two groups. A mixture of VEGF (35.0 µg), bFGF (2.5 µg) and P dGF (3.5 µg) was administered subcutaneously 3, 5 and 7 days to 14 mice before full thickness skin punch biopsy wounding, whereas 14 control animals received three injections of 0.2 ml saline solution. Wound sizes were assessed daily and the repaired tissues were harvested 7 days after complete wound closure. Comp…