المؤلفون: Ilyas Inci, Bart F.J.M. Koopman, Nasim Salehi-Nik, A. K. Kandar, Deepti Rana, Jeroen Rouwkema

المساهمون: Biomechanical Engineering, TechMed Centre

المصدر: Bioactive Materials, 12, 71-84. KeAi Communications Co
Bioactive Materials, Vol 12, Iss, Pp 71-84 (2022)
Bioactive Materials

مصطلحات موضوعية: QH301-705.5, Aptamer, medicine.medical_treatment, Cell, Biomedical Engineering, 02 engineering and technology, Aptamers, Article, Biomaterials, 03 medical and health sciences, medicine, Tissue engineering, Biology (General), Materials of engineering and construction. Mechanics of materials, 030304 developmental biology, 0303 health sciences, Chemistry, Growth factor, Mesenchymal stem cell, Vascularization, Spatiotemporal release, 021001 nanoscience & nanotechnology, Cell biology, medicine.anatomical_structure, Vascular morphogenesis, TA401-492, Vascular endothelial growth factor, Co-culture, 0210 nano-technology, Biotechnology

الوصف: Spatiotemporally controlled growth factor (GF) delivery is crucial for achieving functional vasculature within engineered tissues. However, conventional GF delivery systems show inability to recapitulate the dynamic and heterogeneous nature of developing tissue's biochemical microenvironment. Herein, an aptamer-based programmable GF delivery platform is described that harnesses dynamic affinity interactions for facilitating spatiotemporal control over vascular endothelial GF (VEGF165) bioavailability within gelatin methacryloyl matrices. The platform showcases localized VEGF165 sequestration from the culture medium (offering spatial-control) and leverages aptamer-complementary sequence (CS) hybridization for triggering VEGF165 release (offering temporal-control), without non-specific leakage. Furthermore, extensive 3D co-culture studies (human umbilical vein-derived endothelial cells & mesenchymal stromal cells), in bi-phasic hydrogel systems revealed its fundamentally novel capability to selectively guide cell responses and manipulate lumen-like microvascular networks via spatiotemporally controlling VEGF165 bioavailability within 3D microenvironment. This platform utilizes CS as an external biochemical trigger for guiding vascular morphogenesis which is suitable for creating dynamically controlled engineered tissues.
Graphical abstract Image 1
Highlights • Spatiotemporally controlled VEGF165 bioavailability within bi-phasic acrydite-modified aptamer-functionalized hydrogels. • Aptamer-bound-VEGF165 within bi-phasic hydrogels revealed their ability to selectively guide cell responses. • This unique behavior could be harnessed for regulating vascular morphogenesis within engineered tissues in 4D. • With complementary sequences as an external trigger, dynamically controlled mature microvascular networks were observed.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3301cf8c7bf5f71f7c13a11e0dd5fa01Test
https://research.utwente.nl/en/publications/f84a9947-b0c4-4db9-9afa-314ead1429d2Test

المؤلفون: Sima Stroganov, Michal Elbaz, Raya Eilam, Aviad Cohen, Elena Kartvelishvily, Bareket Dassa, Ofra Golani, Shlomi Lazar, Nava Dekel, Gadi Cohen, Michal Neeman, Eran Gershon, Ron Hadas, Ofir Atrakchi

مصطلحات موضوعية: 0303 health sciences, biology, Angiogenesis, Cell, Trophoblast, Embryo, Early pregnancy factor, Embryonic stem cell, Cell biology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Vascular morphogenesis, embryonic structures, medicine, biology.protein, Receptor, 030304 developmental biology

الوصف: Successful implantation is associated with a unique spatial pattern of vascular remodeling, characterized by profound peripheral neo-vascularization surrounding a peri-embryo avascular niche. We hypothesized that hyaluronan controls the formation of the unique vascular pattern encompassing the embryo. This hypothesis was evaluated by genetic modification of hyaluronan metabolism specifically targeted to embryonic trophoblast cells. The outcome of altered hyaluronan deposition on uterine vascular remodeling and post-implantation development were analyzed by MRI, detailed histological examinations, and RNA-sequencing of uterine NK cells. Our experiments revealed that eliminating the anti-angiogenic hyaluronan, led to elevated expression of MMP-9, VEGF-A and its receptor VEGFR-2, accompanied by reduced recruitment of uterine NK cells. Further local decrease in VEGFR-3 resulted in impaired formation of vascular sinuous folds, ectopic angiogenesis and dysfunctional uterine NK cells. Conversely, enhanced deposition of hyaluronan caused the expansion of the maternal-embryo barrier, leading to an increased diffusion distance and aborted implantation. These results demonstrate a pivotal role for hyaluronan in successful pregnancy by fine-tuning the peri-embryo avascular niche and maternal vascular morphogenesis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::564a514772ec768390f5d4c38db9978fTest
https://doi.org/10.1101/2020.02.09.940544Test

المؤلفون: Laura di Blasio, Marianela Vara-Messler, Luca Primo

المصدر: Biomaterials for 3D Tumor Modeling ISBN: 9780128181287

مصطلحات موضوعية: Endothelial stem cell, Tissue culture, medicine.anatomical_structure, Angiogenic Process, Angiogenesis, Vascular morphogenesis, Cell, medicine, Computational biology, In vitro

الوصف: The formation of new blood vessels is a critical process in several physiological and pathological contexts. The complexity of the angiogenic process is not completely reproducible using standard two-dimensional (2D) culture models. Three-dimensional (3D) models have emerged as effective tools for deciphering molecular mechanisms controlling endothelial cell sprouting and vascular morphogenesis. These models allow dynamic and detailed analysis of the distinct angiogenic steps, as well as molecular manipulation. The “state-of-the-art” in 3D culture models developed for the study of angiogenesis has been review. The potential for 3D cell and tissue culture models to fill the gap between 2D models and clinical application has been assessed. Advances in combining engineering, materials science, and cell biology to highlight the most promising device and microfluidic systems for 3D angiogenesis have also been reported.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eba57ea0aa64c5eb2c8bc0f209e4a3b6Test
https://doi.org/10.1016/b978-0-12-818128-7.00008-3Test

المؤلفون: Moritz Markel, Peter Vajkoczy, Christian Uhl, Thomas Broggini, Melina Nieminen, Irina Kremenetskaia, Marcus Czabanka

المصدر: Angiogenesis

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Physiology, Angiogenesis, Clinical Biochemistry, Tumor microcirculation, Receptor, EphB4, Antiangiogenic therapy, Mice, Nude, Angiogenesis Inhibitors, Apoptosis, Glioblastoma multiforme, 03 medical and health sciences, Intravital microscopy, Mice, 0302 clinical medicine, Glioma, Cell Line, Tumor, medicine, Ephrin, Animals, Humans, Pericyte, Cell Proliferation, Original Paper, Neovascularization, Pathologic, business.industry, EphB4, Neoplasms, Experimental, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Vascular morphogenesis, Cancer research, business

الوصف: Introduction Alterations in vascular morphogenesis are hallmarks of antiangiogenesis-resistant tumor vessels. Vascular morphogenesis is regulated by ephrinB2-EphB4 system which may induce different biological effects depending on the oncological and molecular contexts. It was the aim of the current study to characterize the influence of EphB4 on tumor microcirculation after antiangiogenic treatment using different SF126 glioma models. Materials and methods Using an ecotropic transfection system, empty vector (pLXSN) or EphB4 (EphB4OE) overexpressing Phoenix-ECO cells were coimplanted with SF126 glioma cells subcutaneously (dorsal skinfold chamber, DSC) and orthotopically (cranial window, CW). Tumor volume was assessed by MRI. Intravital microscopy (IVM) allowed microcirculatory analysis (total {TVD} and functional vessel density {FVD}, diameter {D}, and permeability index {PI}) before and after antiangiogenic treatment (Sunitinib: DSC: 40 mg/kg BW, 6 days; CW: 80 mg/kg BW, 4 days). Immunohistochemistry included Pecam–Desmin, Ki67, TUNEL, and Caspase 3 stainings. Results EphB4OE induced large and treatment-resistant tumor vessels (FVD: Control/Su: 110 ± 23 cm/cm2 vs. EphB4OE/Su: 103 ± 42 cm/cm2). Maintenance of pericyte–endothelial cell interactions (Control: 80 ± 12 vs. Control/Su: 47 ± 26%; EphB4OE: 88 ± 9 vs. EphB4OE/Su: 74 ± 25%) and reduced antiproliferative (Control: 637 ± 80 vs. Control/Su: 110 ± 22; EphB4OE: 298 ± 108 vs. EphB4OE/Su: 213 ± 80) and proapoptotic responses (Control: 196 ± 25 vs. Control / Su: 404 ± 60; EphB4OE: 183 ± 20 vs. EphB4OE/Su: 270 ± 66) were observed under EphB4 overexpression. Conclusion EphB4 overexpression leads to vascular resistance by altering vascular morphogenesis, pericyte coverage, and cellular proliferation/apoptosis in experimental SF126 glioma models.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4c2aeba879d12b8031feb8583651e0d6Test
http://europepmc.org/articles/PMC6208883Test

المؤلفون: Barbara Zimmermann, Jorge Andrade, Koraljka Husnjak, Marcus Krüger, Rui Benedito, Yu Ting Ong, Toshiya Sugino, Thomas Boettger, Stefan Guenther, Radiance Lim, Manuel Kaulich, Thomas Braun, Anuradha Doddaballapur, Ivan Dikic, Chenyue Shi, Hendrik Nolte, J. W. D. Fasse, Michael Potente, Andreas Ernst, Klaus Wilhelm

المساهمون: Max Planck Society, European Research Council, Deutsche Forschungsgemeinschaft (Alemania), German Centre for Cardiovascular Research, European Molecular Biology Organization, Publica

المصدر: Repisalud
Instituto de Salud Carlos III (ISCIII)
Science

مصطلحات موضوعية: 0301 basic medicine, Intracellular domain, Endothelium, Notch signaling pathway, Neovascularization, Physiologic, Deubiquitinating enzyme, 03 medical and health sciences, Mice, 0302 clinical medicine, Protein Domains, medicine, Human Umbilical Vein Endothelial Cells, Animals, Humans, RNA, Small Interfering, Receptor, Notch1, Receptor, Mice, Knockout, Multidisciplinary, biology, Chemistry, Protein Stability, Cell biology, 030104 developmental biology, medicine.anatomical_structure, HEK293 Cells, 030220 oncology & carcinogenesis, Vascular morphogenesis, Proteolysis, biology.protein, Ectopic expression, Endothelium, Vascular, Ubiquitin Thiolesterase, Sprouting, Signal Transduction

الوصف: Notch signaling is a core patterning module for vascular morphogenesis that codetermines the sprouting behavior of endothelial cells (ECs). Tight quantitative and temporal control of Notch activity is essential for vascular development, yet the details of Notch regulation in ECs are incompletely understood. We found that ubiquitin-specific peptidase 10 (USP10) interacted with the NOTCH1 intracellular domain (NICD1) to slow the ubiquitin-dependent turnover of this short-lived form of the activated NOTCH1 receptor. Accordingly, inactivation of USP10 reduced NICD1 abundance and stability and diminished Notch-induced target gene expression in ECs. In mice, the loss of endothelial Usp10 increased vessel sprouting and partially restored the patterning defects caused by ectopic expression of NICD1. Thus, USP10 functions as an NICD1 deubiquitinase that fine-tunes endothelial Notch responses during angiogenic sprouting. This work is supported by the Max Planck Society, European Research Council (ERC) starting grant ANGIOMET (311546), ERC consolidator grant EMERGE (773047), the Deutsche Forschungsgemeinschaft (SFB 834), the Excellence Cluster Cardiopulmonary System (EXC 147/1), LOEWE grant Ub-Net, the DZHK (German Center for Cardiovascular Research), the Stiftung Charité, the Cardio-Pulmonary Institute (EXC 2026 project ID 390649896), and the European Molecular Biology Organization (EMBO) Young Investigator Programme Sí

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::535fc52a8a0ccbe7d34024888713ca18Test
http://hdl.handle.net/20.500.12105/9685Test

المؤلفون: Amber N. Stratman

مصطلحات موضوعية: Endothelial stem cell, medicine.anatomical_structure, Chemistry, Vascular morphogenesis, medicine, Tube (fluid conveyance), Pericyte, Cell biology

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::ef29c6eff3f3cf76080001fa86373edbTest
https://doi.org/10.32469/10355/8433Test

المؤلفون: Yanqing A Gong, Hao Duan, Yanling Wang, Yi Fan, Menggui Huang, Zhengqiang He

المصدر: Arteriosclerosis, Thrombosis, and Vascular Biology. 38

مصطلحات موضوعية: Vasculogenesis, medicine.anatomical_structure, Endothelium, Vascular morphogenesis, medicine, Structural integrity, GTPase, Biology, Cardiology and Cardiovascular Medicine, Wound healing, Process (anatomy), Cell biology

الوصف: Vascularization is a fundamental process in development, wound healing, and the progression of cardiovascular diseases. Formation of new blood vessels with functional and structural integrity is crucial for organ growth as well as post-injury tissue repair and regeneration. Although vascular sprouting and outgrowth, i.e. , angiogenesis, has been extensively studied, the underlying mechanisms for vessel formation remain largely unexplored. Here we reveal a critical role of phosphatidylinositol 4,5-bisphosphate (PIP2) for vessel formation in endothelial cells (ECs). Moreover, by using mass spectrometry, our identified Tbc1d2b as a novel PIP2-binding protein in vessel-formatting ECs. Considering its critical function in vessel formation, we name this protein “vesselin”. We showed that vesselin preferentially localizes to blood vessels in various human tissues, and that its siRNA-mediated knockdown inhibits EC tube formation, supporting its major role in vessel formation. Remarkably, injection of inhibitory vesselin morpholino into the embryos blocks blood vessel formation and zebrafish development. Vesselin contains PH (pleckstrin homology) and TBC (Tre2/Bub2/Cdc16) domains, which are known to bind phosphatidylinositols and display GTPase-activating protein (GAP) activities towards Rab GTPases, respectively. Consistently, we found by mass spectrometry that vesselin interacts with the small GTPase Rab13 and small GTPase Rac1. Finally, our further mechanistic studies showed that vesselin interacts with Rac1 and Rab13 during EC vessel formation, and regulates their activity in a PIP2-dependent manner. Thus, we uncover a previously unidentified regulatory system for EC vessel formation, providing molecular resolution of vascular morphogenesis. Targeting vesselin may provide new therapeutic strategies in cardiovascular diseases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::3c7797f66ca324eaf80d6f4f25570e2bTest
https://doi.org/10.1161/atvb.38.suppl_1.674Test

المؤلفون: Tim Vandecasteele, Ward De Spiegelaere, Wim Van Den Broeck, Ingrid Walter, Pieter Cornillie, Anastasia Logothetidou, Waltraud Tschulenk

المصدر: JOURNAL OF VASCULAR RESEARCH

مصطلحات موضوعية: 0301 basic medicine, Endothelium, Physiology, Angiogenesis, Organogenesis, Kidney Glomerulus, Sus scrofa, Neovascularization, Physiologic, Gestational Age, 030226 pharmacology & pharmacy, ANGIOGENESIS, law.invention, MECHANISMS, Extracellular matrix, 03 medical and health sciences, 0302 clinical medicine, KIDNEY, Microscopy, Electron, Transmission, INFLAMMATION, law, medicine, Animals, Intussusceptive angiogenesis, RECONSTRUCTION, Chemistry, MICROVASCULAR GROWTH, Pillar, Endothelial Cells, Biology and Life Sciences, Metanephros, VASCULAR MORPHOGENESIS, Cell biology, Glomerular capillary, Capillaries, Extracellular Matrix, MODEL, 030104 developmental biology, medicine.anatomical_structure, CELLS, Glomerulus, sense organs, Electron microscope, Cardiology and Cardiovascular Medicine, MATRIX, Metanephric kidney, Intraluminal pillar

الوصف: Background/Aims: Intussusceptive angiogenesis (IA) is a dynamic process which contributes to vascular expansion and remodeling. Intraluminal pillars have long been the distinctive structural indicator of IA. However, the mechanism of their formation has not been fully elucidated. Methods: Using light and electron microscopy, we studied intussusceptive vascular growth in the developing porcine metanephric kidney. Results: We observed intraluminal pillars formed by endothelial cells in the vasculature of developing glomeruli. Their diameter was < 2.5 µm, consistent with the diameter of nascent pillars. TEM revealed that the majority of these pillars consisted only of endothelium. However, a central core of extracellular matrix (ECM) covered by endothelium, reminiscent of a more mature intussusceptive pillar, was also found in the lumen of a glomerular capillary. Perivascular cells or pericytes were not involved in the pillar structure during these stages of formation. Conclusion: This study shows ECM presence in a mature intussusceptive pillar without any perivascular cell involvement in the structure. This leads to the hypothesis that ECM deposition precedes the participation of these cells in the formation of intraluminal pillars during IA in porcine metanephric glomerular capillaries.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f89a9e92e924126883493eaef15c712eTest
https://hdl.handle.net/1854/LU-8573905Test

المؤلفون: Stefan Porubsky, Katharina L. Kynast, Krishna Rakesh Sharma, HP Hammes, Sandra J. Stoll, Peter P. Nawroth, Boris Hadaschik, Karen Bieback, Esther Herpel, Jens Kroll, Marlies Elger, Jan-Luuk Hillebrands, Karl Heckler

المساهمون: Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Groningen Institute for Organ Transplantation (GIOT)

المصدر: Scientific Reports
Scientific Reports, 6:37172. Nature Publishing Group

مصطلحات موضوعية: 0301 basic medicine, medicine.medical_specialty, GENETICS, NEPHROPATHY, MIGRATION, MODELS, Kidney development, Apoptosis, Kidney, Article, Nephropathy, Diabetes Mellitus, Experimental, Diabetic nephropathy, PATHWAY, Animals, Genetically Modified, 03 medical and health sciences, Internal medicine, PODOCYTE APOPTOSIS, medicine, Animals, Humans, Zebrafish, Adaptor Proteins, Signal Transducing, COMPLICATIONS, Multidisciplinary, biology, Zebrafish Proteins, medicine.disease, biology.organism_classification, VASCULAR MORPHOGENESIS, Pronephros, 030104 developmental biology, Endocrinology, ELMO1, medicine.anatomical_structure, Renal pathology

الوصف: Engulfment and cell motility 1 (ELMO1) functions as a guanine exchange factor for Rac1 and was recently found to protect endothelial cells from apoptosis. Genome wide association studies suggest that polymorphisms within human elmo1 act as a potential contributing factor for the development of diabetic nephropathy. Yet, the function of ELMO1 with respect to the glomerulus and how this protein contributes to renal pathology was unknown. Thus, this study aimed to identify the role played by ELMO1 in renal development in zebrafish, under hyperglycaemic conditions, and in diabetic nephropathy patients. In zebrafish, hyperglycaemia did not alter renal ELMO1 expression. However, hyperglycaemia leads to pathophysiological and functional alterations within the pronephros, which could be rescued via ELMO1 overexpression. Zebrafish ELMO1 crispants exhibited a renal pathophysiology due to increased apoptosis which could be rescued by the inhibition of apoptosis. In human samples, immunohistochemical staining of ELMO1 in nondiabetic, diabetic and polycystic kidneys localized ELMO1 in glomerular podocytes and in the tubules. However, ELMO1 was not specifically or distinctly regulated under either one of the disease conditions. Collectively, these results highlight ELMO1 as an important factor for glomerular protection and renal cell survival via decreasing apoptosis, especially under diabetic conditions.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e9deb33de2de67cf2ba4b6cce3492bb9Test
http://europepmc.org/articles/PMC5111104Test

المؤلفون: M. L. Iruela-Arispe, R. Vora, Reinhard Fässler, O. D. V. Noel, M. LaRussa, Kirsten A. Turlo, F. Hall-Glenn

المصدر: Developmental Biology. 365:23-35

مصطلحات موضوعية: Aortic arch, Vascular smooth muscle, Neural crest cells, Myocytes, Smooth Muscle, Aorta, Thoracic, Biology, Article, Extracellular matrix, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine.artery, medicine, Animals, Myocyte, Thoracic aorta, Molecular Biology, Aorta, 030304 developmental biology, Extracellular Matrix Proteins, 0303 health sciences, Integrin beta1, Vascular morphogenesis, Gene Expression Regulation, Developmental, Vascular development, Cell Differentiation, Cell Biology, Anatomy, Aortic Aneurysm, Cell biology, Branchial Region, medicine.anatomical_structure, Vascular smooth muscle cell differentiation, Endothelium, Vascular, Gene Deletion, 030217 neurology & neurosurgery, Pharyngeal arch, Developmental Biology

الوصف: β1 integrin has been shown to contribute to vascular smooth muscle cell differentiation, adhesion and mechanosensation in vitro. Here we showed that deletion of β1 integrin at the onset of smooth muscle differentiation resulted in interrupted aortic arch, aneurysms and failure to assemble extracellular matrix proteins. These defects result in lethality prior to birth. Our data indicates that β1 integrin is not required for the acquisition, but it is essential for the maintenance of the smooth muscle cell phenotype, as levels of critical smooth muscle proteins are gradually reduced in mutant mice. Furthermore, while deposition of extracellular matrix was not affected, its structure was disrupted. Interestingly, defects in extracellular matrix and vascular wall assembly, were restricted to the aortic arch and its branches, compromising the brachiocephalic and carotid arteries and to the exclusion of the descending aorta. Additional analysis of β1 integrin in the pharyngeal arch smooth muscle progenitors was performed using wnt1Cre. Neural crest cells deleted for β1 integrin were able to migrate to the pharyngeal arches and associate with endothelial lined arteries; but exhibited vascular remodeling defects and early lethality. This work demonstrates that β1 integrin is dispensable for migration and initiation of the smooth muscle differentiation program, however, it is essential for remodeling of the pharyngeal arch arteries and for the assembly of the vessel wall of their derivatives. It further establishes a critical role of β1 integrin in the protection against aneurysms that is particularly confined to the ascending aorta and its branches.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f25ae5ce0f645e234976e98e645df4cTest
https://doi.org/10.1016/j.ydbio.2012.01.027Test