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Blood outgrowth endothelial cell

David M Kepecs, Darren A Yuen, Yanling Zhang, Kerri Thai, Kim A Connelly, Richard E Gilbert
HYPOTHESIS/INTRODUCTION: Renal fibrovascular injury often persists in chronic kidney disease patients treated with renin-angiotensin system blockers. Intriguingly, early outgrowth cell-derived factor infusion also inhibits chronic renal injury. We sought to determine whether early outgrowth cell-derived factor administration provides further renoprotection when added to renin-angiotensin system blockade. MATERIALS AND METHODS: Conditioned medium was generated by incubating rat early outgrowth cells with serum-free endothelial basal medium-2 to collect their secreted factors...
July 2016: Journal of the Renin-angiotensin-aldosterone System: JRAAS
Hamideh Yadegari, Arijit Biswas, Mohammad Suhail Akhter, Julia Driesen, Vytautas Ivaskevicius, Natascha Marquardt, Johannes Oldenburg
Disease-associated silent mutations are considered to affect the accurate pre-mRNA splicing either by influencing regulatory elements leading to exon skipping or by creating a new cryptic splice site (ss). The present study describes a new molecular pathological mechanism by which a silent mutation inhibits splicing and leads to intron retention. We identified a heterozygous silent mutation c.7464C>T in exon 44 of the von Willebrand factor (VWF) gene in a family with type 1 von Willebrand disease (VWD). In vivo and ex vivo transcript analysis revealed an aberrantly spliced transcript with intron 44 retained in the mRNA, implying disruption of the first catalytic step of splicing at 5' ss...
August 19, 2016: Blood
Igor Cima, Say Li Kong, Debarka Sengupta, Iain B Tan, Wai Min Phyo, Daniel Lee, Min Hu, Ciprian Iliescu, Irina Alexander, Wei Lin Goh, Mehran Rahmani, Nur-Afidah Mohamed Suhaimi, Jess H Vo, Joyce A Tai, Joanna H Tan, Clarinda Chua, Rachel Ten, Wan Jun Lim, Min Hoe Chew, Charlotte A E Hauser, Rob M van Dam, Wei-Yen Lim, Shyam Prabhakar, Bing Lim, Poh Koon Koh, Paul Robson, Jackie Y Ying, Axel M Hillmer, Min-Han Tan
Clusters of tumor cells are often observed in the blood of cancer patients. These structures have been described as malignant entities for more than 50 years, although their comprehensive characterization is lacking. Contrary to current consensus, we demonstrate that a discrete population of circulating cell clusters isolated from the blood of colorectal cancer patients are not cancerous but consist of tumor-derived endothelial cells. These clusters express both epithelial and mesenchymal markers, consistent with previous reports on circulating tumor cell (CTC) phenotyping...
June 29, 2016: Science Translational Medicine
Lindsey Hawke, Mackenzie L Bowman, Man-Chiu Poon, Mary-Frances Scully, Georges-Etienne Rivard, Paula D James
Approximately 10% of von Willebrand factor (VWF) gene mutations are thought to alter messenger RNA (mRNA) splicing through disruption of consensus splice sites. This mechanism is likely underrecognized and affected by mutations outside consensus splice sites. During VWF synthesis, splicing abnormalities lead to qualitative defects or quantitative deficiencies in VWF. This study investigated the pathologic mechanism acting in 3 von Willebrand disease (VWD) families with putative splicing mutations using patient-derived blood outgrowth endothelial cells (BOECs) and a heterologous human embryonic kidney (HEK 293(T)) cell model...
July 28, 2016: Blood
Damien G Noone, Magdalena Riedl, Fred G Pluthero, Mackenzie L Bowman, M Kathryn Liszewski, Lily Lu, Yi Quan, Steve Balgobin, Reinhard Schneppenheim, Sonja Schneppenheim, Ulrich Budde, Paula James, John P Atkinson, Nades Palaniyar, Walter H A Kahr, Christoph Licht
Atypical hemolytic uremic syndrome and thrombotic thrombocytopenic purpura have traditionally been considered separate entities. Defects in the regulation of the complement alternative pathway occur in atypical hemolytic uremic syndrome, and defects in the cleavage of von Willebrand factor (VWF)-multimers arise in thrombotic thrombocytopenic purpura. However, recent studies suggest that both entities are related as defects in the disease-causing pathways overlap or show functional interactions. Here we investigate the possible functional link of VWF-multimers and the complement system on endothelial cells...
July 2016: Kidney International
Karen Bieback, Philipp Netsch
Umbilical cord blood (CB) is considered one of the youngest available sources of adult stem cells. Besides hematopoietic stem cells, CB has been shown to contain endothelial progenitor cells as well as mesenchymal stromal/stem cells (MSC). To isolate MSC from cord blood, CB is collected into a sterile bag containing the anticoagulant citrate-phosphate-dextrose (CPD). The CB is then processed by density-gradient centrifugation to obtain mononuclear cells (MNC). These are cultured until the outgrowth of fibroblastoid cell colonies appears...
2016: Methods in Molecular Biology
Larissa Pfisterer, Thomas Korff
In vitro models mimicking capillary sprouting are important tools to investigate the tumor angiogenesis, developmental blood vessel formation, and pathophysiological remodeling processes of the capillary system in the adult. With this focus, in 1998 Korff et al. introduced endothelial cell (EC) spheroids as a three-dimensional in vitro model resembling angiogenic responses and sprouting behavior [1]. As such, EC spheroids are capable of giving rise to capillary-like sprouts which are relatively close to the physiologically and genetically programmed arrangement of endothelial cells in vessels...
2016: Methods in Molecular Biology
Sonja B Riemenschneider, Donald J Mattia, Jacqueline S Wendel, Jeremy A Schaefer, Lei Ye, Pilar A Guzman, Robert T Tranquillo
A major goal of tissue engineering is the creation of pre-vascularized tissues that have a high density of organized microvessels that can be rapidly perfused following implantation. This is especially critical for highly metabolic tissues like myocardium, where a thick myocardial engineered tissue would require rapid perfusion within the first several days to survive transplantation. In the present work, tissue patches containing human microvessels that were either randomly oriented or aligned were placed acutely on rat hearts post-infarction and for each case it was determined whether rapid inosculation could occur and perfusion of the patch could be maintained for 6 days in an infarct environment...
August 2016: Biomaterials
Brahim Chaqour
CCN1 is encoded by an extracellular matrix protein-gene that is essential for the proper development of the cardiovascular system and the control of angiogenesis, inflammation, progenitor cell lineage commitment and extracellular matrix protein remodeling during the adult life. High-precision genetic models of tissue-specific gene deletion demonstrated a pivotal role of CCN1 in providing positional information to angiogenic endothelial cells (ECs) during the outgrowth and maturation of nascent blood vessel sprouts, fine-controlling Notch-dependent inter-endothelial cell communications and mediating interaction with inflammatory cells...
May 4, 2016: Journal of Cell Communication and Signaling
Dieter Dauwe, Beatriz Pelacho, Arief Wibowo, Ann-Sophie Walravens, Kristoff Verdonck, Hilde Gillijns, Ellen Caluwe, Peter Pokreisz, Nick van Gastel, Geert Carmeliet, Maarten Depypere, Frederik Maes, Nina Vanden Driessche, Walter Droogne, Johan Van Cleemput, Johan Vanhaecke, Felipe Prosper, Catherine Verfaillie, Aernout Luttun, Stefan Janssens
BACKGROUND: Blood outgrowth endothelial cells (BOECs) mediate therapeutic neovascularization in experimental models, but outgrowth characteristics and functionality of BOECs from patients with ischemic cardiomyopathy (ICMP) are unknown. We compared outgrowth efficiency and in vitro and in vivo functionality of BOECs derived from ICMP with BOECs from age-matched (ACON) and healthy young (CON) controls. METHODS AND RESULTS: We isolated 3.6±0.6 BOEC colonies/100×10(6) mononuclear cells (MNCs) from 60-mL blood samples of ICMP patients (n=45; age: 66±1 years; LVEF: 31±2%) versus 3...
April 2016: Journal of the American Heart Association
Jéssica de Souza Sanches, Rodrigo Barbosa de Aguiar, Carolina Bellini Parise, Juliana Mayumi Suzuki, Roger Chammas, Jane Zveiter de Moraes
Tumors require blood supply and, to overcome this restriction, induce angiogenesis. Vascular endothelial growth factor (VEGF) plays an important role in this process, which explains the great number of antiangiogenic therapies targeting VEGF. The research and development of targeted therapy has led to the approval of bevacizumab, a humanized anti-VEGF monoclonal antibody (mAb), in clinical settings. However, side effects have been reported, usually as a consequence of bolus-dose administration of the antibody...
April 2016: Cancer Science
Juhyun Lee, Peng Fei, René R Sevag Packard, Hanul Kang, Hao Xu, Kyung In Baek, Nelson Jen, Junjie Chen, Hilary Yen, C-C Jay Kuo, Neil C Chi, Chih-Ming Ho, Rongsong Li, Tzung K Hsiai
Hemodynamic shear forces are intimately linked with cardiac development, during which trabeculae form a network of branching outgrowths from the myocardium. Mutations that alter Notch signaling also result in trabeculation defects. Here, we assessed whether shear stress modulates trabeculation to influence contractile function. Specifically, we acquired 4D (3D + time) images with light sheets by selective plane illumination microscopy (SPIM) for rapid scanning and deep axial penetration during zebrafish morphogenesis...
May 2, 2016: Journal of Clinical Investigation
Yang Shi, Fanlu Wang, Sanjay Tiwari, Meran Yesilbas, Nadine Steubesand, Jan-Tobias Weitkamp, Tim Klüter, Sebastian Lippross, David Eglin, Andreas Seekamp, Sabine Fuchs
Engineering of a vascularized bone construct is a highly challenging task which needs to take into account the impact of different components on the bone regeneration process. Bone repair influencing factors in such constructs range from the material properties and scaffold design, to the interaction of different cell types contributing to bone formation and remodeling or neovascularization, respectively. In this context, early endothelial progenitor cells (EPC,) mononuclear cells isolated from the peripheral blood, express the endothelial marker CD31 but also a series of myeloid markers and have been shown to support the formation of vessel-like structures...
March 4, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Francesco Paneni, Sarah Costantino, Nicolle Kränkel, Francesco Cosentino, Thomas F Lüscher
AIMS: Impaired tissue vascularization is a major determinant of cardiovascular disease (CVD) in the elderly. Accumulation of reactive oxygen species (ROS) may interfere with vascular repair, but the underlying mechanisms remain unknown. Early outgrowth cells (EOCs) play an important role in endothelial repair. We investigated whether key lifespan genes involved in ROS, i.e. the mitochondrial adaptor p66(Shc) and the AP-1 transcription factor JunD, contribute to age-related EOCs dysfunction in humans...
June 7, 2016: European Heart Journal
Kazuko Goto, Genzou Takemura, Tomoyuki Takahashi, Hideshi Okada, Hiromitsu Kanamori, Itta Kawamura, Takatomo Watanabe, Kentaro Morishita, Akiko Tsujimoto, Nagisa Miyazaki, Hiroaki Ushikoshi, Masanori Kawasaki, Atsushi Mikami, Ken-ichiro Kosai, Shinya Minatoguchi
When injected directly into ischemic tissue in patients with peripheral artery disease, the reparative capacity of endothelial progenitor cells (EPCs) appears to be limited by their poor survival. We, therefore, attempted to improve the survival of transplanted EPCs through intravenous injection and gene modification. We anticipated that overexpression of integrin β1 will enable injected EPCs to home to ischemic tissue, which abundantly express extracellular matrix proteins, the ligands for integrins. In addition, integrin β1 has an independent angiogenesis-stimulating function...
February 2016: Stem Cells Translational Medicine
Maria Mitsi, Martin Michael Peter Schulz, Epameinondas Gousopoulos, Alexandra Michaela Ochsenbein, Michael Detmar, Viola Vogel
Angiogenesis and lymphangiogenesis are highly complex morphogenetic processes, central to many physiological and pathological conditions, including development, cancer metastasis, inflammation and wound healing. While it is described that extracellular matrix (ECM) fibers are involved in the spatiotemporal regulation of angiogenesis, current angiogenesis assays are not specifically designed to dissect and quantify the underlying molecular mechanisms of how the fibrillar nature of ECM regulates vessel sprouting...
2015: PloS One
H A Mena, A Carestia, L Scotti, F Parborell, M Schattner, S Negrotto
UNLABELLED: ESSENTIALS: Extracellular histones are highly augmented in sites of neovessel formation, such as regeneration tissues. We studied histone effect on survival and angiogenic activity of mature and progenitor endothelial cells. Extracellular histones trigger apoptosis and pyroptosis and reduce angiogenesis in vivo and in vitro. Histone blockade can be useful as a therapeutic strategy to improve angiogenesis and tissue regeneration. BACKGROUND: Extracellular histones are highly augmented in sites of neovessel formation, like regeneration tissues...
February 2016: Journal of Thrombosis and Haemostasis: JTH
Rhandy M Eman, Henriette A W Meijer, F Cumhur Öner, Wouter J A Dhert, Jacqueline Alblas
Vascularization is crucial for the induction of bone formation. In this study, we investigated the application of two subtypes of peripheral blood-derived endothelial progenitor cells (EPCs) to stimulate vessel formation in ectopic bone constructs. Early and late outgrowth EPCs (E-EPC and L-EPC, respectively) were characterized for their ability to form network structures in vitro and perfused vessels subcutaneously in mice. Only L-EPCs showed the formation of fully connected networks on Matrigel two-dimensional (2D) angiogenesis assays...
February 2016: Tissue Engineering. Part A
Darren A Yuen, David M Kepecs, Yanling Zhang, Suzanne Advani, Kerri Thai, Kim A Connelly, Richard E Gilbert
BACKGROUND: Bone marrow-derived early outgrowth cells (EOCs) secrete soluble factors that exert potent renoprotective effects, such that infusion of their conditioned medium recapitulates the affects of the cells themselves. OBJECTIVES: The objective of this study is to test whether the protective effect of conditioned medium infusion wanes with time and whether tachyphylaxis occurs with repeated administration. DESIGN: This is a placebo-controlled animal study...
2015: Canadian Journal of Kidney Health and Disease
Lara Bou Khzam, Olivier Bouchereau, Rahma Boulahya, Ahmed Hachem, Younes Zaid, Haissam Abou-Saleh, Yahye Merhi
BACKGROUND: Endothelial progenitor cells (EPCs) have been implicated in neoangiogenesis, endothelial repair and cell-based therapies for cardiovascular diseases. We have previously shown that the recruitment of EPCs to sites of vascular lesions is facilitated by platelets where EPCs, in turn, modulate platelet function and thrombosis. However, EPCs encompass a heterogeneous population of progenitor cells that may exert different effects on platelet function. Recent evidence suggests the existence of two EPC subtypes: early outgrowth cells (EOCs) and endothelial colony-forming cells (ECFCs)...
2015: Journal of Translational Medicine
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