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endothelial heterogeneity

Morio Ueno, Kazuko Asada, Munetoyo Toda, Asako Hiraga, Monty Montoya, Chie Sotozono, Shigeru Kinoshita, Junji Hamuro
Purpose: To elucidate a noninvasive method to qualify and identify cultured human corneal endothelial cells (cHCECs) devoid of cell-state transition and adaptable for cell-based therapy. Methods: The variations of cHCECs in their composition of heterogeneous subpopulations (SPs) were verified in relation to their surface cluster-of-differentiation (CD) markers and their morphology. The profiles of microRNA (miRNA) in cultured cells or supernatants were detected by 3D-Gene Human microRNA Chips (Toray Industries, Inc...
October 1, 2016: Investigative Ophthalmology & Visual Science
S J Lang, D Böhringer, G Geerling, T Reinhard
AimThe objective of the study was to evaluate the long-term results of allogenic penetrating limbo-keratoplasy. This method allows simultaneous transplantation of a corneal graft and limbal stem cells of the donor by means of eccentric trephination of the donor button.MethodThe data of 192 consecutive cases of allogenic penetrating limbo-keratoplasty from 1995 to 2015 were reviewed. These had been performed exclusively in eyes with complete failure of the limbal stem cells, in combination with deep corneal scarring...
October 21, 2016: Eye
Leslie A Blair, April K Haven, Natalie N Bauer
BACKGROUND: Microparticles (MPs) stimulate inflammatory adhesion molecule expression in systemic vascular diseases, however it is unknown whether circulating MPs stimulate localized ICAM-1 expression in the heterogeneically distinct pulmonary endothelium during pulmonary arterial hypertension (PAH). Pulmonary vascular lesions with infiltrating inflammatory cells in PAH form in the pulmonary arteries and arterioles, but not the microcirculation. Therefore, we sought to determine whether circulating MPs from PAH stimulate pulmonary artery endothelial cell-selective ICAM-1 expression...
October 20, 2016: Respiratory Research
James J Hsieh, David Chen, Patricia I Wang, Mahtab Marker, Almedina Redzematovic, Ying-Bei Chen, S Duygu Selcuklu, Nils Weinhold, Nancy Bouvier, Kety H Huberman, Umesh Bhanot, Michael S Chevinsky, Parul Patel, Patrizia Pinciroli, Helen H Won, Daoqi You, Agnes Viale, William Lee, A Ari Hakimi, Michael F Berger, Nicholas D Socci, Emily H Cheng, Jennifer Knox, Martin H Voss, Maurizio Voi, Robert J Motzer
BACKGROUND: Metastatic renal cell carcinoma (RCC) patients are commonly treated with vascular endothelial growth factor (VEGF) inhibitors or mammalian target of rapamycin inhibitors. Correlations between somatic mutations and first-line targeted therapy outcomes have not been reported on a randomized trial. OBJECTIVE: To evaluate the relationship between tumor mutations and treatment outcomes in RECORD-3, a randomized trial comparing first-line everolimus (mTOR inhibitor) followed by sunitinib (VEGF inhibitor) at progression with the opposite sequence in 471 metastatic RCC patients...
October 14, 2016: European Urology
Junji Hamuro, Morio Ueno, Kazuko Asada, Munetoyo Toda, Monty Montoya, Chie Sotozono, Shigeru Kinoshita
Purpose: To clarify whether cultured human corneal endothelial cells (cHCECs), heterogeneous in their differentiation state, exhibit distinctive energy metabolism with the aim to develop a reliable method to sort cHCECs applicable for regenerative medicine. Methods: The presence of cHCEC subpopulations (SPs) was verified via surface cluster-of-differentiation (CD) marker expression. Cultured HCEC metabolic extracts or corresponding culture supernatants with distinctive cellular phenotypes in regard to energy-metabolism-related functional markers c-Myc and CD44 were prepared and analyzed via capillary electrophoresis-tandem mass spectrometry...
August 1, 2016: Investigative Ophthalmology & Visual Science
Jimmy Hwang
Esophagogastric cancers (EGCa) are a leading cause of cancer related mortality worldwide. It has been recognized that they represent heterogenous diseases based on histology and anatomy. However, it is also increasingly evident that these are diverse malignancies based on genetic alterations, and this is increasingly making these diseases amenable to targeted therapies. While epidermal growth factor receptor (EGFR) and mTOR inhibitors have failed to prove effective in the treatment of advanced EGCa, vascular endothelial growth factor (VEGF) inihibitor have now been demonstrated to improve survival, at least in the 2nd line setting of adenocarcinomas...
October 2016: Journal of Gastrointestinal Oncology
Sophie Guelfi, Hugues Duffau, Luc Bauchet, Bernard Rothhut, Jean-Philippe Hugnot
Glioblastomas are devastating and extensively vascularized brain tumors from which glioblastoma stem-like cells (GSCs) have been isolated by many groups. These cells have a high tumorigenic potential and the capacity to generate heterogeneous phenotypes. There is growing evidence to support the possibility that these cells are derived from the accumulation of mutations in adult neural stem cells (NSCs) as well as in oligodendrocyte progenitors. It was recently reported that GSCs could transdifferentiate into endothelial-like and pericyte-like cells both in vitro and in vivo, notably under the influence of Notch and TGFβ signaling pathways...
2016: Stem Cells International
Siddharth Shanbhag, Kamal Mustafa, Nikolaos Pandis, Jens R Nyengaard, Andreas Stavropoulos
The regenerative potential of tissue engineered bone constructs may be enhanced by in vitro co-culture and in vivo co-transplantation of vasculogenic and osteogenic (progenitor) cells. The objective of this study was to systematically review the literature to answer the focused question: in animal models, does co-transplantation of osteogenic and vasculogenic cells enhance bone regeneration in craniofacial defects, compared to solely osteogenic cell-seeded constructs? Following PRISMA guidelines, electronic databases were searched for controlled animal studies reporting co-transplantation of endothelial cells (EC) with mesenchymal stem cells (MSC) or osteoblasts (OB) in craniofacial critical-size bone defect (CSD) models...
October 12, 2016: Tissue Engineering. Part B, Reviews
Marta Prieto-Vila, Ting Yan, Anna Sanchez Calle, Neha Nair, Laura Hurley, Tomonari Kasai, Hiroki Kakuta, Junko Masuda, Hiroshi Murakami, Akifumi Mizutani, Masaharu Seno
To grow beyond a size of approximately 1-2 mm(3), tumor cells activate many processes to develop blood vasculature. Growing evidences indicate that the formation of the tumor vascular network is very complex, and is not restricted to angiogenesis. Cancer cell-derived tumor vasculatures have been recently described. Among them, endothelial differentiation of tumor cells have been directly related to cancer stem cells, which are cells within a tumor that possess the capacity to self-renew, and to exhibit multipotential heterogeneous lineages of cancer cells...
2016: American Journal of Cancer Research
Karen Beets, Michael W Staring, Nathan Criem, Elke Maas, Niels Schellinx, Susana M Chuva de Sousa Lopes, Lieve Umans, An Zwijsen
BACKGROUND: Bone morphogenetic protein (BMP) signalling has emerged as a fundamental pathway in endothelial cell biology and deregulation of this pathway is implicated in several vascular disorders. BMP signalling output in endothelial cells is highly context- and dose-dependent. Phosphorylation of the BMP intracellular effectors, SMAD1/5/9, is routinely used to monitor BMP signalling activity. To better understand the in vivo context-dependency of BMP-SMAD signalling, we investigated differences in BMP-SMAD transcriptional activity in different vascular beds during mouse embryonic and postnatal stages...
October 10, 2016: BMC Developmental Biology
Elena Cambria, Julia Steiger, Julia Günter, Annina Bopp, Petra Wolint, Simon P Hoerstrup, Maximilian Y Emmert
Cardiac stem cell therapy holds great potential to prompt myocardial regeneration in patients with ischemic heart disease. The selection of the most suitable cell type is pivotal for its successful application. Various cell types, including crude bone marrow mononuclear cells, skeletal myoblast, and hematopoietic and endothelial progenitors, have already advanced into the clinical arena based on promising results from different experimental and preclinical studies. However, most of these so-called first-generation cell types have failed to fully emulate the promising preclinical data in clinical trials, resulting in heterogeneous outcomes and a critical lack of translation...
July 2016: Transfusion Medicine and Hemotherapy
Elisabeth Naschberger, Andrea Liebl, Vera S Schellerer, Manuela Schütz, Nathalie Britzen-Laurent, Patrick Kölbel, Ute Schaal, Lisa Haep, Daniela Regensburger, Thomas Wittmann, Ludger Klein-Hitpass, Tilman T Rau, Barbara Dietel, Valérie S Méniel, Alan R Clarke, Susanne Merkel, Roland S Croner, Werner Hohenberger, Michael Stürzl
Different tumor microenvironments (TMEs) induce stromal cell plasticity that affects tumorigenesis. The impact of TME-dependent heterogeneity of tumor endothelial cells (TECs) on tumorigenesis is unclear. Here, we isolated pure TECs from human colorectal carcinomas (CRCs) that exhibited TMEs with either improved (Th1-TME CRCs) or worse clinical prognosis (control-TME CRCs). Transcriptome analyses identified markedly different gene clusters that reflected the tumorigenic and angiogenic activities of the respective TMEs...
October 10, 2016: Journal of Clinical Investigation
Nathalie Nielsen, Christoffer Laustsen, Lotte Bonde Bertelsen
Endothelial progenitor cells (EPCs) represent a heterogeneous cell population that is believed to be involved in vasculogenesis. With the purpose of enhancing endothelial repair, EPCs could have a potential for future cell therapies. Due to the low amount of EPCs in the peripheral circulating blood, in vitro expansion is needed before administration to recipients and the effects of in vitro culturing is still an under-evaluated field with little knowledge of how the cells change over time in culture. The aim of this study was to use hyperpolarised carbon-13 magnetic resonance spectroscopy to profile important metabolic pathways in a population of progenitor cells and to show that cell culturing in 3D scaffolds seem to block the metabolic processes that leads to cell senescence...
October 5, 2016: Experimental Cell Research
Albert Busch, Elena Hartmann, Caroline Grimm, Süleyman Ergün, Ralph Kickuth, Christoph Otto, Richard Kellersmann, Udo Lorenz
OBJECTIVE: Abdominal aortic aneurysm (AAA) is a frequent, potentially life-threatening, disease that can only be treated by surgical means such as open surgery or endovascular repair. No alternative treatment is currently available, and despite expanding knowledge about the pathomechanism, clinical trials on medical aneurysm abrogation have led to inconclusive results. The heterogeneity of human AAA based on histologic examination is thereby generally neglected. In this study we aimed to further elucidate the role of these differences in aneurysm disease...
October 5, 2016: Journal of Vascular Surgery
Soyeon Lee, Hyo Gyoung Kang, Jin Eun Choi, Jang Hyuck Lee, Hyo Jung Kang, Sun Ah Baek, Eungbae Lee, Yangki Seok, Won Kee Lee, Shin Yup Lee, Seung Soo Yoo, Jaehee Lee, Seung Ick Cha, Chang Ho Kim, Sukki Cho, Jae Yong Park
Vascular endothelial growth factor (VEGF) contributes to tumor angiogenesis. The role of VEGF single nucleotide polymorphisms (SNPs) in lung cancer susceptibility and its prognosis remains inconclusive and controversial. This study was performed to investigate whether VEGF polymorphisms affect survival outcomes of patients with early stage non-small cell lung cancer (NSCLC) after surgery. Three potentially functional VEGF SNPs (rs833061T>C, rs2010963G>C, and rs3025039C>T) were genotyped. A total of 782 NSCLC patients who were treated with surgical resection were enrolled...
November 2016: Journal of Korean Medical Science
Lin Xiao, Andrew C Dudley
In the heart and other organs, endothelial-mesenchymal transition (EndMT) has emerged as an important developmental process that involves coordinated migration, differentiation, and proliferation of the endothelium. In multiple disease states including cancer angiogenesis and cardiovascular disease, the processes that regulate EndMT are recapitulated, albeit in an uncoordinated and dysregulated manner. Members of the transforming growth factor beta (TGFβ) super-family are well known to impart cellular plasticity during EndMT by the timely activation (or repression) of transcription factors and miRNAs in addition to epigenetic regulation of gene expression...
October 4, 2016: Journal of Pathology
Fabien Lavocat, Laura Maggi, Francesco Annunziato, Pierre Miossec
OBJECTIVE: To compare the direct effect of cytokines on synoviocytes and endothelial cells to the effects of supernatants from Th1, Th17 and Th1/17 clones and the direct cell-cell interactions with the same clones. METHODS: Th17 and Th1/17 clones were obtained from the CD161+CCR6+ fraction and Th1 clones from the CD161-CCR6- fraction of human CD4+ T-cells. Endothelial cells or synoviocytes were cultured in the presence of either isolated pro-inflammatory cytokines (IL-17 and/or TNF-α) or supernatants from the T-cell clones or co-cultured with T-cell clones themselves...
December 2016: Cytokine
Verónica Torres-Estay, Daniela V Carreño, Patricia Fuenzalida, Anica Watts, Ignacio F San Francisco, Viviana P Montecinos, Paula C Sotomayor, John Ebos, Gary J Smith, Alejandro S Godoy
BACKGROUND: Sex-related differences in the role of androgen have been reported in cardiovascular diseases and angiogenesis. Moreover, androgen receptor (AR) has been causally involved in the homeostasis of human prostate endothelial cells. However, levels of expression, functionality and biological role of AR in male- and female-derived human endothelial cells (ECs) remain poorly characterized. The objectives of this work were (1) to characterize the functional expression of AR in male- and female-derived human umbilical vein endothelial cell (HUVEC), and (2) to specifically analyze the biological effects of DHT, and the role of AR on these effects, in male-derived HUVECs (mHUVECs)...
September 27, 2016: Angiogenesis
Marc P McRae
OBJECTIVE: l-Arginine is a semi-essential amino acid that is the substrate for nitric oxide production by vascular endothelial and immune cells. Nitric oxide production by these cells is essential for both blood pressure regulation and immune regulation. However, there is much discrepancy in the literature when it comes to randomized controlled studies, and so this umbrella review of published meta-analyses was performed to examine the efficacy of l-arginine's role as a therapeutic agent...
September 2016: Journal of Chiropractic Medicine
Eliza L S Fong, Daniel A Harrington, Mary C Farach-Carson, Hanry Yu
Numerous studies to date have contributed to a paradigm shift in modeling cancer, moving from the traditional two-dimensional culture system to three-dimensional (3D) culture systems for cancer cell culture. This led to the inception of tumor engineering, which has undergone rapid advances over the years. In line with the recognition that tumors are not merely masses of proliferating cancer cells but rather, highly complex tissues consisting of a dynamic extracellular matrix together with stromal, immune and endothelial cells, significant efforts have been made to better recapitulate the tumor microenvironment in 3D...
November 2016: Biomaterials
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