Publications
464 results found
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".
Harding S, 2011, European perspectives in cardiology, Circulation, Vol: 123, ISSN: 0009-7322
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
Foeldes G, Harding SE, 2011, Stem Cell Therapy to Treat Heart Failure, COMPREHENSIVE BIOTECHNOLOGY, VOL 5: MEDICAL BIOTECHNOLOGY AND HEALTHCARE, 2ND EDITION, Editors: MooYoung, Publisher: ELSEVIER SCIENCE BV, Pages: 407-423
Rao C, Ali NA, Athanasiou T, et al., 2011, Phenotype and Developmental Potential of Cardiomyocytes from Induced Pluripotent Stem Cells and Human Embryonic Stem Cells, Nuclear Reprogramming and Stem Cells, Editors: Ainscough, Yamanaka, Tada, Berlin Heidelberg, Publisher: Humana Press, ISBN: 978-1-61779-224-3
Research into the field of stem cell biology has developed exponentially over recent years, and is beginning to offer significant promise for unravelling the molecular basis of a multitude of disease states. Importantly, in addition to offering the opportunity to delve deeply into the mechanisms that drive disease aetiology the research is realistically opening the doors for development of targeted and personalized therapeutic applications that many considered, until recently, to be nothing more that a far fetched dream. This volume provides a timely glimpse into the methods that have been developed to instigate, and the mechanisms that have been identified to drive, the process of nuclear reprogramming, chronicling how the field has developed over the last 50-60 years. Since the early 1950s a small number of notable experiments have provided significant impetus to the field, primarily the demonstration of reprogramming ability, first by the complex cytoplasmic milieu that constitutes the amphibian egg, then that of the mammalian egg, and finally that of the mammalian embryonic stem cell. Most recently, the demonstration that a limited pool of defined molecules is capable of reprogramming a multitude of cell types has provided massive impetus and facilitated transition towards realistic therapeutic application. We have therefore reproduced some of the key articles that elegantly document these dramatic stages of development of the field in an inclusive appendix to the book, for the benefit of readers keen to investigate the history of how the field of stem cell biology has evolved. Owing to the ever broadening nature of this field, and the incredible rate at which it is evolving, the main content of this volume focuses on areas that have shown significant movement in recent years, are most likely to translate into personalized therapeutic application, and thus provide greatest potential for significant impact on human health in the not too distant future. We recogni
Harding SE, 2011, Human stem cell-derived cardiomyocytes for pharmacological and toxicological modeling, ANIMAL MODELS: THEIR VALUE IN PREDICTING DRUG EFFICACY AND TOXICITY, Vol: 1245, Pages: 48-49, ISSN: 0077-8923
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- Citations: 3
Jawad H, El Fray M, Boccaccini AR, et al., 2010, Nanocomposite Elastomeric Biomaterials for Myocardial Tissue Engineering Using Embryonic Stem Cell-derived Cardiomyocytes, Conference on Materials Science and Engineering (MSE), Publisher: WILEY-V C H VERLAG GMBH, Pages: B664-B674, ISSN: 1438-1656
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- Citations: 9
Harding SE, 2010, Frontiers in Cardiovascular Biology: a new federation of European scientists., Future Cardiol, Vol: 6, Pages: 765-767
Stuckey DJ, Ishii H, Chen Q-Z, et al., 2010, Magnetic Resonance Imaging Evaluation of Remodeling by Cardiac Elastomeric Tissue Scaffold Biomaterials in a Rat Model of Myocardial Infarction, TISSUE ENGINEERING PART A, Vol: 16, Pages: 3395-3402, ISSN: 1937-3341
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- Citations: 65
Song W, Dyer E, Stuckey D, et al., 2010, Investigation of a transgenic mouse model of familial dilated cardiomyopathy, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol: 49, Pages: 380-389, ISSN: 0022-2828
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- Citations: 48
Rees PSC, Davidson SM, Harding SE, et al., 2010, The mitochondrial permeability transition pore is a functional target for cardioprotection in human hypertrophic cardiomyopathy, ESC Congress, Publisher: OXFORD UNIV PRESS, Pages: 925-925, ISSN: 0195-668X
Sato M, Carr CA, Stuckey DJ, et al., 2010, Functional and Morphological Maturation of Implanted Neonatal Cardiomyocytes as a Comparator for Cell Therapy, STEM CELLS AND DEVELOPMENT, Vol: 19, Pages: 1025-1034, ISSN: 1547-3287
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- Citations: 4
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
Paur HE, Nikolaev V, Lyon A, et al., 2010, Stress cardiomyopathy: a role for stimulus trafficking at the beta-2 adrenoceptor in cardiac depression?, Conference on Frontiers in Cardiovascular Biology, Publisher: OXFORD UNIV PRESS, Pages: S127-S127, ISSN: 0008-6363
Lyon AR, Bannister ML, Coward E, et al., 2010, STABILISATION OF SR LEAK IN HEART FAILURE AFTER SERCA2A GENE THERAPY, Annual Conference and Exhibition of the British-Cardiovascular-Society, Publisher: B M J PUBLISHING GROUP, Pages: A10-A10, ISSN: 1355-6037
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.
Chen Q-Z, Ishii H, Thouas GA, et al., 2010, An elastomeric patch derived from poly(glycerol sebacate) for delivery of embryonic stem cells to the heart, BIOMATERIALS, Vol: 31, Pages: 3885-3893, ISSN: 0142-9612
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- Citations: 141
Lyon AR, Bannister ML, Kohlbrenner E, et al., 2010, Stabilisation of SR Leak in Heart Failure After SERCA2a Gene Therapy, 7th Annual Conference of the British-Society-for-Gene-Therapy, Publisher: MARY ANN LIEBERT INC, Pages: 503-503, ISSN: 1043-0342
Nikolaev VO, Moshkov A, Lyon AR, et al., 2010, Beta2-adrenergic receptor redistribution in heart failure changes cAMP compartmentation., Science (New York, N.Y.), Vol: 327, Pages: 1653-7
The beta1- and beta2-adrenergic receptors (betaARs) on the surface of cardiomyocytes mediate distinct effects on cardiac function and the development of heart failure by regulating production of the second messenger cyclic adenosine monophosphate (cAMP). The spatial localization in cardiomyocytes of these betaARs, which are coupled to heterotrimeric guanine nucleotide-binding proteins (G proteins), and the functional implications of their localization have been unclear. We combined nanoscale live-cell scanning ion conductance and fluorescence resonance energy transfer microscopy techniques and found that, in cardiomyocytes from healthy adult rats and mice, spatially confined beta2AR-induced cAMP signals are localized exclusively to the deep transverse tubules, whereas functional beta1ARs are distributed across the entire cell surface. In cardiomyocytes derived from a rat model of chronic heart failure, beta2ARs were redistributed from the transverse tubules to the cell crest, which led to diffuse receptor-mediated cAMP signaling. Thus, the redistribution of beta(2)ARs in heart failure changes compartmentation of cAMP and might contribute to the failing myocardial phenotype.
Lompre A-M, Hajjar RJ, Harding SE, et al., 2010, Ca<SUP>2+</SUP> Cycling and New Therapeutic Approaches for Heart Failure, CIRCULATION, Vol: 121, Pages: 822-830, ISSN: 0009-7322
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- Citations: 93
Song W, Stuckey DJ, Dyer E, et al., 2010, PHENOTYPE OF THE ACTC E99K TRANSGENIC MOUSE REPRODUCES HYPERTROPHIC CARDIOMYOPATHY IN PATIENTS, Conference on Myocardial Energetics and Redox in Health and Disease, Publisher: B M J PUBLISHING GROUP, ISSN: 1355-6037
Bannister ML, Scoote M, Kingsbury MP, et al., 2010, Phosphorylation of Excitation-Contraction Coupling Components in a Guinea-Pig Model of Heart Failure, BIOPHYSICAL JOURNAL, Vol: 98, Pages: 302A-303A, ISSN: 0006-3495
Lyon AR, Coward E, Dubb S, et al., 2009, Stabilisation of SR Leak in Heart Failure After SERCA2a Gene Therapy, 82nd Scientific Session of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: S688-S689, ISSN: 0009-7322
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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- Citations: 26
Lyon AR, MacLeod KT, Zhang Y, et al., 2009, Loss of T-tubules and other changes to surface topography in ventricular myocytes from failing human and rat heart, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 106, Pages: 6854-6859, ISSN: 0027-8424
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- Citations: 279
Sato M, Kerton A, Harding SE, 2009, Refinement of <i>in vivo</i> surgical procedures for cardiac gene and cell transfer in rats, LAB ANIMAL, Vol: 38, Pages: 94-101, ISSN: 0093-7355
Song W, Stuckey DJ, Dyer E, et al., 2009, Mouse HCM Model Expressing E99K ACTC Mutation Reproduces Phenotypes As Found In Human Patients, Publisher: CELL PRESS, Pages: 499A-500A, ISSN: 0006-3495
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- Citations: 1
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