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Bradley P Kropp - One of the best experts on this subject based on the ideXlab platform.
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enhanced Angiogenesis of modified porcine small intestinal submucosa with hyaluronic acid poly lactide co glycolide nanoparticles from fabrication to preclinical validation
Journal of Biomedical Materials Research Part A, 2010Co-Authors: Fadee G Mondalek, Richard A Ashley, Christopher C Roth, Yusuf Kibar, Nabeel Shakir, Michael A Ihnat, Kar Ming Fung, Brian P Grady, Bradley P KroppAbstract:Hyaluronic acid-poly(de-co-glycolide) nanoparticles (HA-PLGA NPs) were synthesized to stabilize the porous structure of porcine small intestinal submucosa (SIS), to improve surface biocompatibility and to enhance performance in tissue regeneration. HA-PLGA NPs were characterized for size, zeta potential, surface morphology, and HA loading. Human microvascular endothelial cells responded to HA-PLGA NPs and HA-PLGA modified SIS (HA-PLGA-SIS) with elevated cell proliferation. HA-PLGA-SIS significantly enhanced neo-vascularization in an in ovo chorioallantoic membrane Angiogenesis Model. The angiogenic capability of the newly fabricated HA-PLGA-SIS was tested in a canine bladder augmentation Model. Urinary bladder augmentation was performed in beagle dogs following hemi-cystectomy using HA-PLGA-SIS. The regenerated bladder was harvested at 10 weeks post augmentation and vascularization was evaluated using CD31 immunohistochemical staining. Bladder regenerated with HA-PLGA-SIS had significantly higher vascular ingrowth compared to unmodified SIS. This study shows that HA-PLGA NPs may represent a new approach for modifying naturally derived SIS biomaterials in regenerative medicine.
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enhanced Angiogenesis of modified porcine small intestinal submucosa with hyaluronic acid poly lactide co glycolide nanoparticles from fabrication to preclinical validation
Journal of Biomedical Materials Research Part A, 2010Co-Authors: Fadee G Mondalek, Richard A Ashley, Christopher C Roth, Yusuf Kibar, Nabeel Shakir, Michael A Ihnat, Kar Ming Fung, Brian P Grady, Bradley P KroppAbstract:Hyaluronic acid-poly(de-co-glycolide) nanoparticles (HA-PLGA NPs) were synthesized to stabilize the porous structure of porcine small intestinal submucosa (SIS), to improve surface biocompatibility and to enhance performance in tissue regeneration. HA-PLGA NPs were characterized for size, zeta potential, surface morphology, and HA loading. Human microvascular endothelial cells responded to HA-PLGA NPs and HA-PLGA modified SIS (HA-PLGA-SIS) with elevated cell proliferation. HA-PLGA-SIS significantly enhanced neo-vascularization in an in ovo chorioallantoic membrane Angiogenesis Model. The angiogenic capability of the newly fabricated HA-PLGA-SIS was tested in a canine bladder augmentation Model. Urinary bladder augmentation was performed in beagle dogs following hemi-cystectomy using HA-PLGA-SIS. The regenerated bladder was harvested at 10 weeks post augmentation and vascularization was evaluated using CD31 immunohistochemical staining. Bladder regenerated with HA-PLGA-SIS had significantly higher vascular ingrowth compared to unmodified SIS. This study shows that HA-PLGA NPs may represent a new approach for modifying naturally derived SIS biomaterials in regenerative medicine. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
Fadee G Mondalek - One of the best experts on this subject based on the ideXlab platform.
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enhanced Angiogenesis of modified porcine small intestinal submucosa with hyaluronic acid poly lactide co glycolide nanoparticles from fabrication to preclinical validation
Journal of Biomedical Materials Research Part A, 2010Co-Authors: Fadee G Mondalek, Richard A Ashley, Christopher C Roth, Yusuf Kibar, Nabeel Shakir, Michael A Ihnat, Kar Ming Fung, Brian P Grady, Bradley P KroppAbstract:Hyaluronic acid-poly(de-co-glycolide) nanoparticles (HA-PLGA NPs) were synthesized to stabilize the porous structure of porcine small intestinal submucosa (SIS), to improve surface biocompatibility and to enhance performance in tissue regeneration. HA-PLGA NPs were characterized for size, zeta potential, surface morphology, and HA loading. Human microvascular endothelial cells responded to HA-PLGA NPs and HA-PLGA modified SIS (HA-PLGA-SIS) with elevated cell proliferation. HA-PLGA-SIS significantly enhanced neo-vascularization in an in ovo chorioallantoic membrane Angiogenesis Model. The angiogenic capability of the newly fabricated HA-PLGA-SIS was tested in a canine bladder augmentation Model. Urinary bladder augmentation was performed in beagle dogs following hemi-cystectomy using HA-PLGA-SIS. The regenerated bladder was harvested at 10 weeks post augmentation and vascularization was evaluated using CD31 immunohistochemical staining. Bladder regenerated with HA-PLGA-SIS had significantly higher vascular ingrowth compared to unmodified SIS. This study shows that HA-PLGA NPs may represent a new approach for modifying naturally derived SIS biomaterials in regenerative medicine.
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enhanced Angiogenesis of modified porcine small intestinal submucosa with hyaluronic acid poly lactide co glycolide nanoparticles from fabrication to preclinical validation
Journal of Biomedical Materials Research Part A, 2010Co-Authors: Fadee G Mondalek, Richard A Ashley, Christopher C Roth, Yusuf Kibar, Nabeel Shakir, Michael A Ihnat, Kar Ming Fung, Brian P Grady, Bradley P KroppAbstract:Hyaluronic acid-poly(de-co-glycolide) nanoparticles (HA-PLGA NPs) were synthesized to stabilize the porous structure of porcine small intestinal submucosa (SIS), to improve surface biocompatibility and to enhance performance in tissue regeneration. HA-PLGA NPs were characterized for size, zeta potential, surface morphology, and HA loading. Human microvascular endothelial cells responded to HA-PLGA NPs and HA-PLGA modified SIS (HA-PLGA-SIS) with elevated cell proliferation. HA-PLGA-SIS significantly enhanced neo-vascularization in an in ovo chorioallantoic membrane Angiogenesis Model. The angiogenic capability of the newly fabricated HA-PLGA-SIS was tested in a canine bladder augmentation Model. Urinary bladder augmentation was performed in beagle dogs following hemi-cystectomy using HA-PLGA-SIS. The regenerated bladder was harvested at 10 weeks post augmentation and vascularization was evaluated using CD31 immunohistochemical staining. Bladder regenerated with HA-PLGA-SIS had significantly higher vascular ingrowth compared to unmodified SIS. This study shows that HA-PLGA NPs may represent a new approach for modifying naturally derived SIS biomaterials in regenerative medicine. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
Masayuki Imamura - One of the best experts on this subject based on the ideXlab platform.
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vascular endothelial growth factor reduces mural cell coverage of endothelial cells and induces sprouting rather than luminal division in an ht1080 tumour Angiogenesis Model
International Journal of Experimental Pathology, 2004Co-Authors: Akihisa Fujimoto, Hisashi Onodera, Akira Mori, Naoki Isobe, Seiichi Yasuda, Yoshikuni Yonenaga, Tsuyoshi Tachibana, Masayuki ImamuraAbstract:Vascular endothelial growth factor (VEGF) plays a central role in tumour Angiogenesis. In a mouse intramuscular tumour Model using VEGF-transfected HT1080 human fibrosarcoma, we investigated the morphological features and patterns of reModelling in size-matched tumours. Compared with the control tumours (C group), the VEGF-transfected tumours (V group) showed vigorous neovascularization with larger vessels. Fenestrations and disruptions of endothelia were specific to the V group. Three types of vascular reModelling, i.e. sprouting, luminal division and intussusceptive microvascular growth, were present in both groups. Morphometric analyses revealed that mural cell coverage of the endothelial cells was significantly smaller in the V group compared with that in the C group (V group, 28.2 +/- 18.6%; C group, 41.6 +/- 21.1%; P < 0.0001). To determine the prevalence of reModelling patterns, the occurrences of abluminal and luminal processes on endothelial cell surfaces were quantified. Abluminal processes are defined as cytoplasmic protrusions of the abluminal membrane of endothelial cells, which can vary from tiny spurs to solid sprouts of the cell. On the other hand, luminal processes are defined as intraluminal protrusions of the endothelial cell membrane, including various membranous changes from filiform processes to rather thick cytoplasmic bulges. An abluminal process is thought to represent an initial morphological change in sprouting type Angiogenesis, and a luminal process to be a sign of implementation of luminal division. The frequency of abluminal processes was significantly higher in the V group than in the C group (V group, 0.243 +/- 0.138/microm; C group, 0.114 +/- 0.101/microm; P < 0.0001). In contrast, the number of luminal processes on the endothelial cells per micrometre was statistically comparable between the groups (V group, 0.285 +/- 0.252/microm; C group, 0.309 +/- 0.236/microm, P = 0.381). These results indicate that sprouting is the main mode of VEGF-induced tumour Angiogenesis.
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vascular endothelial growth factor reduces mural cell coverage of endothelial cells and induces sprouting rather than luminal division in an ht1080 tumour Angiogenesis Model
International Journal of Experimental Pathology, 2004Co-Authors: Akihisa Fujimoto, Hisashi Onodera, Akira Mori, Naoki Isobe, Seiichi Yasuda, Yoshikuni Yonenaga, Tsuyoshi Tachibana, Hideaki Oe, Masayuki ImamuraAbstract:As Angiogenesis plays a critical role in tumour growth, a precise understanding of the morphological features as well as the molecular mechanisms involved in tumour Angiogenesis is necessary to develop better therapeutic strategies. Morphologically, two aspects are of great importance in Angiogenesis: (1) the contact between pericytes and endothelial cells and (2) the types of vascular reModelling, i.e. sprouting, intussusception and luminal division. There have been many reports suggesting that pericytes play an important role in Angiogenesis and vascular maturity. Withdrawal of pericytes occurs prior to endothelial cell proliferation in an adult rat cardiac and skeletal muscle Angiogenesis Model, suggesting that pericytes exert an inhibitory effect on endothelial cell proliferation (Egginton et al. 1996). Similarly, pericyte coverage of the vascular endothelium brings vessel maturation and marks the end of the plastic state of immature vessels (Benjamin et al. 1998). Currently, three distinct Models of vascular morphogenesis and reModelling have been recognized in various settings of Angiogenesis. Sprouting is the most conventional type of Angiogenesis and most frequently used to evaluate Angiogenesis both in vitro and in vivo. Capillary sprouts originate as small endothelial spurs, which eventually grow to form anastomoses with other sprouts and create functional capillary loops (Rhodin & Fujita 1989). The other two modes of Angiogenesis basically involve intraluminal splitting of the blood vessels that expand the blood flow by increasing the number of blood vessels in situ. Intussusceptive microvascular growth (IMG) refers to vascular reModelling by insertion of tissue pillars or interstitial tissue structures (ITSs) into the vascular lumen, resulting in partitioning of the vessel lumen (Caduff et al. 1986; Patan et al. 1996a). Despite having a similar reModelling pattern to IMG, luminal division is another distinct type of intraluminal reModelling in that this does not require interstitial tissue intrusion from outside the vessel wall at the early phase of implementation. Luminal division begins with small intraluminal processes or vacuolization of endothelial cells without any morphological change of the abluminal surface that grows to divide the vessel lumen into segments (Zhou et al. 1998). There are several factors that affect the pattern of Angiogenesis. For example, the polarity of mechanical stimuli to the endothelial cells, i.e. intraluminal or abluminal stimulation, determines which mode of Angiogenesis occurs (Egginton et al. 2001). In relation to growth factors, little is known as to which type of Angiogenesis is preferentially induced under a certain kind of growth factor regime. Vascular endothelial growth factor (VEGF) is a potent modulator of vascular endothelial cells. There are a vast amount of data reported to date, showing that VEGF acts as a vascular permeability factor as well as a mitogen and a survival factor of endothelial cells. Although it has been taken for granted that capillary sprouting is the prime mode of VEGF-induced Angiogenesis, no such quantitative data have been published so far that compared the frequency of sprouting and other types of Angiogenesis on the basis of the intensity of VEGF expression in the same tumour Model. Previously, we reported that VEGF promoted tumourigenicity and metastasis by inducing tumour Angiogenesis in hepatocellular carcinoma and colorectal tumours (Mise et al. 1996; Ishigami et al. 2000; Kondo et al. 2000a) as well as in VEGF-overexpressing tumour cell Models in mice (Mori et al. 1999; Kondo et al. 2000b). In the present study, focusing on the role of VEGF in the tumour Angiogenesis, we evaluated the morphological interaction between endothelial cells and mural cells, and quantified the frequency of abluminal and luminal processes on the plasmalemmal membrane of endothelial cells that potentially lead to sprouting or luminal division in a VEGF-induced tumour Angiogenesis Model.
Kar Ming Fung - One of the best experts on this subject based on the ideXlab platform.
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enhanced Angiogenesis of modified porcine small intestinal submucosa with hyaluronic acid poly lactide co glycolide nanoparticles from fabrication to preclinical validation
Journal of Biomedical Materials Research Part A, 2010Co-Authors: Fadee G Mondalek, Richard A Ashley, Christopher C Roth, Yusuf Kibar, Nabeel Shakir, Michael A Ihnat, Kar Ming Fung, Brian P Grady, Bradley P KroppAbstract:Hyaluronic acid-poly(de-co-glycolide) nanoparticles (HA-PLGA NPs) were synthesized to stabilize the porous structure of porcine small intestinal submucosa (SIS), to improve surface biocompatibility and to enhance performance in tissue regeneration. HA-PLGA NPs were characterized for size, zeta potential, surface morphology, and HA loading. Human microvascular endothelial cells responded to HA-PLGA NPs and HA-PLGA modified SIS (HA-PLGA-SIS) with elevated cell proliferation. HA-PLGA-SIS significantly enhanced neo-vascularization in an in ovo chorioallantoic membrane Angiogenesis Model. The angiogenic capability of the newly fabricated HA-PLGA-SIS was tested in a canine bladder augmentation Model. Urinary bladder augmentation was performed in beagle dogs following hemi-cystectomy using HA-PLGA-SIS. The regenerated bladder was harvested at 10 weeks post augmentation and vascularization was evaluated using CD31 immunohistochemical staining. Bladder regenerated with HA-PLGA-SIS had significantly higher vascular ingrowth compared to unmodified SIS. This study shows that HA-PLGA NPs may represent a new approach for modifying naturally derived SIS biomaterials in regenerative medicine.
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enhanced Angiogenesis of modified porcine small intestinal submucosa with hyaluronic acid poly lactide co glycolide nanoparticles from fabrication to preclinical validation
Journal of Biomedical Materials Research Part A, 2010Co-Authors: Fadee G Mondalek, Richard A Ashley, Christopher C Roth, Yusuf Kibar, Nabeel Shakir, Michael A Ihnat, Kar Ming Fung, Brian P Grady, Bradley P KroppAbstract:Hyaluronic acid-poly(de-co-glycolide) nanoparticles (HA-PLGA NPs) were synthesized to stabilize the porous structure of porcine small intestinal submucosa (SIS), to improve surface biocompatibility and to enhance performance in tissue regeneration. HA-PLGA NPs were characterized for size, zeta potential, surface morphology, and HA loading. Human microvascular endothelial cells responded to HA-PLGA NPs and HA-PLGA modified SIS (HA-PLGA-SIS) with elevated cell proliferation. HA-PLGA-SIS significantly enhanced neo-vascularization in an in ovo chorioallantoic membrane Angiogenesis Model. The angiogenic capability of the newly fabricated HA-PLGA-SIS was tested in a canine bladder augmentation Model. Urinary bladder augmentation was performed in beagle dogs following hemi-cystectomy using HA-PLGA-SIS. The regenerated bladder was harvested at 10 weeks post augmentation and vascularization was evaluated using CD31 immunohistochemical staining. Bladder regenerated with HA-PLGA-SIS had significantly higher vascular ingrowth compared to unmodified SIS. This study shows that HA-PLGA NPs may represent a new approach for modifying naturally derived SIS biomaterials in regenerative medicine. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
Christopher C.w. Hughes - One of the best experts on this subject based on the ideXlab platform.
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the requirement for fibroblasts in Angiogenesis fibroblast derived matrix proteins are essential for endothelial cell lumen formation
Molecular Biology of the Cell, 2011Co-Authors: Andrew C Newman, Martin N. Nakatsu, Wayne Chou, Paul D Gershon, Christopher C.w. HughesAbstract:A role for fibroblasts in physiological and pathological Angiogenesis is now well recognized; however, the precise mechanisms underlying their action have not been deter- mined. Using an in vitro Angiogenesis Model in combination with a candidate gene approach, column chromatography, and mass spectrometry, we identify two classes of fibroblast-de - rived factors—one that supports vessel sprouting but not lumen formation, and one that promotes lumen formation. In the absence of fibroblasts a combination of angiopoietin-1, angiogenin, hepatocyte growth factor, transforming growth factor-α, and tumor necrosis fac- tor drives robust endothelial cell (EC) sprouting; however, lumens fail to form. Subsequent addition of fibroblast-conditioned medium restores lumenogenesis. Using small interfering RNA-mediated knockdown, we show that five genes expressed in fibroblasts—collagen I, procollagen C endopeptidase enhancer 1, secreted protein acidic and rich in cysteine, trans - forming growth factor-β-induced protein ig-h3, and insulin growth factor-binding protein 7—are necessary for lumen formation. Moreover, lumen formation can be rescued by addi - tion of purified protein to knockdown cultures. Finally, using rheology, we demonstrate that the presence of these matricellular proteins results in significantly stiffer gels, which corre - lates with enhanced lumen formation. These findings highlight the critical role that fibroblast- derived extracellular matrix components play in EC lumen formation and provide potential insight into the role of fibroblasts in the tumor microenvironment.
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VEGF 121 and VEGF 165 Regulate Blood Vessel Diameter Through Vascular Endothelial Growth Factor Receptor 2 in an in vitro Angiogenesis Model
Laboratory Investigation, 2003Co-Authors: Martin N. Nakatsu, Richard C.a. Sainson, Sofía Pérez-del-pulgar, Jason Aoto, Mark Aitkenhead, Kevin L. Taylor, Philip M. Carpenter, Christopher C.w. HughesAbstract:Vascular endothelial growth factor (VEGF) is essential for the induction of Angiogenesis and drives both endothelial cell (EC) proliferation and migration. It has been suggested that VEGF also regulates vessel diameter, although this has not been tested explicitly. The two most abundant isoforms, VEGF121 and VEGF165, both signal through VEGF receptor 2 (VEGFR-2). We recently optimized a three-dimensional in vitro Angiogenesis assay using HUVECs growing on Cytodex beads and embedded in fibrin gels. Fibroblasts provide critical factors that promote sprouting, lumen formation, and vessel stability. Using this assay, we have examined the role of VEGF in setting vessel diameter. Low concentrations of both VEGF121 and VEGF165 promote growth of long, thin vessels, whereas higher concentrations of VEGF remarkably enhance vessel diameter. Placental growth factor, which binds to VEGFR-1 but not VEGFR-2, does not promote capillary sprouting. Moreover, specific inhibition of VEGFR-2 signaling results in a dramatic reduction of EC sprouting in response to VEGF, indicating the critical importance of this receptor. The increase in vessel diameter is the result of cell proliferation and migration, rather than cellular hypertrophy, and likely depends on MEK1-ERK1/2 signaling. Both phosphatidylinositol 3-kinase and p38 activity are required for cell survival. We conclude that the diameter of new capillary sprouts can be determined by the local concentration of VEGF and that the action of VEGF on angiogenic EC in this assay is critically dependent on signaling through VEGFR-2.