72 results found
Foldes G, Matsa E, Kriston-Vizi J, et al., 2014, Aberrant alpha-Adrenergic Hypertrophic Response in Cardiomyocytes from Human Induced Pluripotent Cells, Stem Cell Reports, Vol: 3, Pages: 905-914, ISSN: 2213-6711
Semjeni M, Foldes G, Szigeti K, et al., 2014, ROLE OF IN VIVO IMAGING IN CARDIVASCULAR RESEARCH, DIAGNOSIS AND TREATMENT, 82nd Congress of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, Pages: E300-E300, ISSN: 0021-9150
Foldes G, Gara E, Lendvai Z, et al., 2014, Signalling via pi3k/foxo1a pathway modulates formation and survival of human embryonic stem cell-derived endothelial cells, CARDIOVASCULAR RESEARCH, Vol: 103, ISSN: 0008-6363
Gara E, Skopal J, Kosztin A, et al., 2014, Angiogenic potential of human pluripotent stem cell-derived arterial and venous endothelial cells, CARDIOVASCULAR RESEARCH, Vol: 103, ISSN: 0008-6363
Hellen N, Wheeler JX, Ricardo CP, et al., 2014, Effect of T3 on human induced pluripotent stem cell-derived cardiomyocyte maturation, CARDIOVASCULAR RESEARCH, Vol: 103, ISSN: 0008-6363
Reed DM, Foldes G, Gatheral T, et al., 2014, Pathogen Sensing Pathways in Human Embryonic Stem Cell Derived-Endothelial Cells: Role of NOD1 Receptors, PLOS One, Vol: 9, ISSN: 1932-6203
Human embryonic stem cell-derived endothelial cells (hESC-EC), as well as other stem cell derived endothelial cells, have a range of applications in cardiovascular research and disease treatment. Endothelial cells sense Gram-negative bacteria via the pattern recognition receptors (PRR) Toll-like receptor (TLR)-4 and nucleotide-binding oligomerisation domain-containing protein (NOD)-1. These pathways are important in terms of sensing infection, but TLR4 is also associated with vascular inflammation and atherosclerosis. Here, we have compared TLR4 and NOD1 responses in hESC-EC with those of endothelial cells derived from other stem cells and with human umbilical vein endothelial cells (HUVEC). HUVEC, endothelial cells derived from blood progenitors (blood outgrowth endothelial cells; BOEC), and from induced pluripotent stem cells all displayed both a TLR4 and NOD1 response. However, hESC-EC had no TLR4 function, but did have functional NOD1 receptors. In vivo conditioning in nude rats did not confer TLR4 expression in hESC-EC. Despite having no TLR4 function, hESC-EC sensed Gram-negative bacteria, a response that was found to be mediated by NOD1 and the associated RIP2 signalling pathways. Thus, hESC-EC are TLR4 deficient but respond to bacteria via NOD1. This data suggests that hESC-EC may be protected from unwanted TLR4-mediated vascular inflammation, thus offering a potential therapeutic advantage.
Foeldes G, Mioulane M, Kodagoda T, et al., 2014, Immunosuppressive Agents Modulate Function, Growth, and Survival of Cardiomyocytes and Endothelial Cells Derived from Human Embryonic Stem Cells, STEM CELLS AND DEVELOPMENT, Vol: 23, Pages: 467-476, ISSN: 1547-3287
Foldes G, Matsa E, Kriston-Vizi J, et al., 2013, Key differences in hypertrophic signalling between hESC- and hIPSC-derived cardiomyocytes, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 279-279, ISSN: 0195-668X
Foldes G, Matsa E, Kriston-Vizi J, et al., 2013, Key differences in hypertrophic signalling in hESC-and hIPSC-derived cardiomyocytes, Conference of the British-Society-for-Gene-and-Cell-Therapy (BSGCT), Publisher: MARY ANN LIEBERT INC, Pages: A9-A9, ISSN: 1043-0342
Reed DM, Kirkby NS, Foldes G, et al., 2013, Prostacyclin release pathways in stem cell derived endothelial cells, Experimental Biology 2013
Reed DM, Foldes G, Gashaw HH, et al., 2013, Conditioning of human embryonic stem cell-derived endothelial cells with PBMCs confers TLR4 sensing in co-culture conditions, Experimental Biology 2013
Ebner N, Foeldes G, Szabo T, et al., 2013, Assessment of serum cotinine in patients with chronic heart failure: self-reported versus objective smoking behaviour, CLINICAL RESEARCH IN CARDIOLOGY, Vol: 102, Pages: 95-101, ISSN: 1861-0684
Földes G, Mioulane M, 2013, High-content imaging and analysis of pluripotent stem cell-derived cardiomyocytes., Methods Mol Biol, Vol: 1052, Pages: 29-39
Human pluripotent stem cells (hPSC) are investigated as a source of authentic human cardiac cells for drug discovery and toxicological tests. Cell-based assays using automated fluorescence imaging platform and high-content analysis characterize hypertrophic and toxicity profiles of compounds in hPSC-derived cardiomyocytes (hPSC-CM) at the cellular and subcellular levels. In purified population of hPSC-CM loaded with cell tracer probe and cell death markers, both hypertrophic and toxicity profiles can be assessed in live cardiomyocyte cultures. Alternatively, in non-purified cultures of hPSC-CM, hypertrophy, proliferation, and cell death assays can be performed specifically in the cardiomyocyte subpopulation using antibodies directed against cardiac proteins and a combination of cell death- and proliferation-specific fluorescent probes.
Mioulane M, Foldes G, Ali NN, et al., 2012, Development of high content imaging methods for cell death detection in human pluripotent stem cell-derived cardiomyocytes, Journal of Cardiovascular Translational Research, Vol: 5, Pages: 593-604, ISSN: 1937-5387
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CM) are being investigated as a new source of cardiac cells for drug safety assessment. We developed a novel scalable high content microscopy-based method for the detection of cell death in hPSC-CM that can serve for future predictive in vitro cardio-toxicological screens. Using rat neonatal ventricular cardiomyocytes (RVNC) or hPSC-CM, assays for nuclear remodelling, mitochondrial status, apoptosis and necrosis were designed using a combination of fluorescent dyes and antibodies on an automated microscopy platform. This allowed the observation of a chelerythrine-induced concentration-dependent apoptosis to necrosis switch and time-dependent progression of early apoptotic cells towards a necrotic-like phenotype. Susceptibility of hPSC-CM to chelerythrine-stimulated apoptosis varied with time after differentiation, but at most time points, hPSC-CM were more resistant than RVNC. This simple and scalable humanized high-content assay generates accurate cardiotoxicity profiles that can serve as a base for further assessment of cardioprotective strategies and drug safety.
Mioulane M, Foldes G, Harding S, 2012, Cardiomyocytes from Human Pluripotent Stem Cells Predict Chemotherapy-Induced Cardiotoxicity, Basic Cardiovascular Sciences Scientific Session, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7330
Ebner N, Foldes G, Schomburg L, et al., 2012, Lipopolysaccharide Responsiveness is an Independent Predictor of Death in Chronic Heart Failure, 16th Annual Scientific Meeting of the Heart-Failure-Society-of-America, Publisher: CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS, Pages: S26-S26, ISSN: 1071-9164
Reed DM, Foldes G, Harding SE, et al., 2012, Stem cell derived endothelial cells for cardiovascular disease; a therapeutic perspective., British Journal of Clinical Pharmacology
Foldes G, Maxime M, Ali NN, et al., 2012, Modulating cell survival of human embryonic stem cell derivatives by immunosuppressive drugs, 2nd Congress of the European-Society-of-Cardiology Council on Basic Cardiovascular Science - Frontiers in Cardiovascular Biology, Publisher: OXFORD UNIV PRESS, Pages: S99-S99, ISSN: 0008-6363
Foldes G, Bagyura Z, Lendvai Z, et al., 2012, Transplantation of human embryonic stem cell-derived endothelial cells into rats: a new approach for vascular regeneration, 2nd Congress of the European-Society-of-Cardiology Council on Basic Cardiovascular Science - Frontiers in Cardiovascular Biology, Publisher: OXFORD UNIV PRESS, Pages: S16-S17, ISSN: 0008-6363
Mioulane M, Foldes G, Harding SE, 2012, Cardiotoxicity of chemotherapeutic agents assessed in human embryonic or induced pluripotent stem cell-derived cardiomyocytes, 2nd Congress of the European-Society-of-Cardiology Council on Basic Cardiovascular Science - Frontiers in Cardiovascular Biology, Publisher: OXFORD UNIV PRESS, Pages: S47-S47, ISSN: 0008-6363
Foldes G, Mioulane M, Chahine MN, et al., 2011, HUMAN INDUCED PLURIPOTENT STEM CELL-DERIVED CARDIOMYOCYTES SERVE AS IN VITRO MODEL OF CARDIAC HYPERTROPHY (Retracted article. See vol. 99, pg. 00, 2013), HEART, Vol: 97, Pages: 11-11, ISSN: 1355-6037
Chahine MN, Mioulane M, Foldes G, et al., 2011, NUCLEAR PROTEIN IMPORT MEDIATES PHENYLEPHRINE-INDUCED HYPERTROPHY IN ADULT AND HUMAN EMBRYONIC STEM CELL-DERIVED CARDIOMYOCYTES, HEART, Vol: 97, Pages: 10-10, ISSN: 1355-6037
Reed DM, Foldes G, Gatheral T, et al., 2011, ENDOTHELIN-1 RELEASE FROM HUMAN EMBRYONIC STEM CELL DERIVED-ENDOTHELIAL CELLS (HESC-EC): COMPARISONS WITH HUMAN ENDOTHELIAL CELLS, 10th World Congress on Inflammation, Publisher: BIRKHAUSER VERLAG AG, Pages: 224-224, ISSN: 1023-3830
Reed DM, Foldes G, Badiger RV, et al., 2011, TLR3 AND INTERFERON FUNCTION IN HUMAN EMBRYONIC STEM CELL-DERIVED ENDOTHELIAL CELLS (HESC-EC): RELEVANCE TO VIRAL IMMUNITY, Heart
Földes G, Mioulane M, Wright JS, et al., 2011, Modulation of human embryonic stem cell-derived cardiomyocyte growth: a testbed for studying human cardiac hypertrophy?, Journal of molecular and cellular cardiology, Vol: 50, Pages: 367-76, ISSN: 1095-8584
Human embryonic stem cell-derived cardiomyocytes (hESC-CM) are being developed for tissue repair and as a model system for cardiac physiology and pathophysiology. However, the signaling requirements of their growth have not yet been fully characterized. We showed that hESC-CM retain their capacity for increase in size in long-term culture. Exposing hESC-CM to hypertrophic stimuli such as equiaxial cyclic stretch, angiotensin II, and phenylephrine (PE) increased cell size and volume, percentage of hESC-CM with organized sarcomeres, levels of ANF, and cytoskeletal assembly. PE effects on cell size were separable from those on cell cycle. Changes in cell size by PE were completely inhibited by p38-MAPK, calcineurin/FKBP, and mTOR blockers. p38-MAPK and calcineurin were also implicated in basal cell growth. Inhibitors of ERK, JNK, and CaMK II partially reduced PE effects; PKG or GSK3β inhibitors had no effect. The role of p38-MAPK was confirmed by an additional pharmacological inhibitor and adenoviral infection of hESC-CM with a dominant-inhibitory form of p38-MAPK. Infection of hESC-CM with constitutively active upstream MAP2K3b resulted in an increased cell size, sarcomere and cytoskeletal assembly, elongation of the cells, and induction of ANF mRNA levels. siRNA knockdown of p38-MAPK inhibited PE-induced effects on cell size. These results reveal an important role for active protein kinase signaling in hESC-CM growth and hypertrophy, with potential implications for hESC-CM as a novel in vitro test system. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".
Foldes G, Ali NN, Randi A, et al., 2011, PATHOGEN SENSING PATHWAYS IN HUMAN STEM CELL-DERIVED ENDOTHELIAL CELLS, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 4-4, ISSN: 1073-2322
Foldes G, Mioulane M, Iqbal A, et al., 2010, Growth and proliferative activity of human embryonic stem cell-derived cardiomyocytes is modulated in a calcineurin-NFAT-dependent manner, Conference on Frontiers in Cardiovascular Biology, Publisher: OXFORD UNIV PRESS, Pages: S111-S111, ISSN: 0008-6363
Mioulane M, Foldes G, Ali NN, et al., 2010, Cardiomyocytes derived from human embryonic stem cells as an alternative model for cardiotoxicity and contractility studies., Conference on Frontiers in Cardiovascular Biology, Publisher: OXFORD UNIV PRESS, Pages: S110-S110, ISSN: 0008-6363
Foeldes G, Liu A, Badiger R, et al., 2010, Innate Immunity in Human Embryonic Stem Cells: Comparison with Adult Human Endothelial Cells, PLOS ONE, Vol: 5, ISSN: 1932-6203
Treatment of human disease with human embryonic stem cell (hESC)-derived cells is now close to reality, but little is known of their responses to physiological and pathological insult. The ability of cells to respond via activation of Toll like receptors (TLR) is critical in innate immune sensing in most tissues, but also extends to more general danger sensing, e.g. of oxidative stress, in cardiomyocytes. We used biomarker release and gene-array analysis to compare responses in hESC before and after differentiation, and to those in primary human endothelial cells. The presence of cardiomyocytes and endothelial cells was confirmed in differentiated cultures by immunostaining, FACS-sorting and, for cardiomyocytes, beating activity. Undifferentiated hESC did not respond with CXCL8 release to Gram positive or Gram negative bacteria, or a range of PAMPs (pathogen associated molecular patterns) for TLRs 1-9 (apart from flagellin, an activator of TLR5). Surprisingly, lack of TLR-dependent responses was maintained over 4 months of differentiation of hESC, in cultures which included cardiomyocytes and endothelial cells. In contrast, primary cultures of human aortic endothelial cells (HAEC) demonstrated responses to a broad range of PAMPs. Expression of downstream TLR signalling pathways was demonstrated in hESC, and IL-1β, TNFα and INFγ, which bypass the TLRs, stimulated CXCL8 release. NFκB pathway expression was also present in hESC and NFκB was able to translocate to the nucleus. Low expression levels of TLRs were detected in hESC, especially TLRs 1 and 4, explaining the lack of response of hESC to the main TLR signals. TLR5 levels were similar between differentiated hESC and HAEC, and siRNA knockdown of TLR5 abolished the response to flagellin. These findings have potential implications for survival and function of grafted hESC-derived cells.
Kadir SHSA, Ali NN, Mioulane M, et al., 2009, Embryonic stem cell-derived cardiomyocytes as a model to study fetal arrhythmia related to maternal disease, JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Vol: 13, Pages: 3730-3741
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