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Cardiomyocyte stem cells

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https://www.readbyqxmd.com/read/28735524/characterization-of-cytoskeleton-features-and-maturation-status-of-cultured-human-ipsc-derived-cardiomyocytes
#1
Christian Zuppinger, George Gibbons, Priyanka Dutta-Passecker, Adrian Segiser, Henriette Most, Thomas M Suter
Recent innovations in stem cell technologies and the availability of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have opened new possibilities for studies and drug testing on human cardiomyocytes in vitro. Still, there are concerns about the precise nature of such 'reprogrammed' cells. We have performed an investigation using immunocytochemistry and confocal microscopy on several cellular features using commercially available hiPSC-CMs. For some selected developmentally regulated or cardiac chamber-specific proteins, we have compared the results from hiPSC-derived cardiomyocytes with freshly isolated, ventricular cardiomyocytes from adult rats...
June 21, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28733255/nanofiber-structured-hydrogel-yarns-with-ph-response-capacity-and-cardiomyocyte-drivability-for-bio-microactuator-application
#2
Shaohua Wu, Bin Duan, Xiaohong Qin, Jonathan T Butcher
Polymeric hydrogels have great potential in soft biological micro-actuator applications. However, inappropriate micro-architecture, non-anisotropy, weak biomechanics, and inferior response behaviors limit their development. In this study, we designed and manufactured novel polyacrylonitrile (PAN)-based hydrogel yarns composed with uniaxially aligned nanofibers. The nanofibrous hydrogel yarns possessed anisotropic architecture and robust mechanical properties with flexibility, and could be assembled into defined scaffold structures by subsequent processes...
July 18, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28731525/differences-in-stem-cell-processing-lead-to-distinct-secretomes-secretion-implications-for-differential-results-of-previous-clinical-trials-of-stem-cell-therapy-for-myocardial-infarction
#3
Bernhard Wernly, Inês Gonçalves, Attila Kiss, Vera Paar, Tobias Mösenlechner, Michael Leisch, David Santer, Lucas Motloch, Klaus Ulrich Klein, Eva Verena Tretter, Daniel Kretzschmar, Bruno Podesser, Christian Jung, Uta C Hoppe, Michael Lichtenauer
INTRODUCTION: Stem cell therapy for acute myocardial infarction (AMI) seemed to be a promising therapy, however large clinical trials brought differential outcome. It has been shown that paracrine effects of secretomes of stem cells rather than cell therapy might play a fundamental role. The present study sought to compare cell processing protocols of clinical trials and investigated effects of differential cell culture conditions on chemokine secretion and functional effects. METHODS: Different secretomes were compared regarding IL-8, VEGF, MCP-1 and TNF-alpha secretion...
July 21, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28729840/cardiac-subtype-specific-modeling-of-kv1-5-ion-channel-deficiency-using-human-pluripotent-stem-cells
#4
Maike Marczenke, Ilaria Piccini, Isabella Mengarelli, Jakob Fell, Albrecht Röpke, Guiscard Seebohm, Arie O Verkerk, Boris Greber
The ultrarapid delayed rectifier K(+) current (IKur), mediated by Kv1.5 channels, constitutes a key component of the atrial action potential. Functional mutations in the underlying KCNA5 gene have been shown to cause hereditary forms of atrial fibrillation (AF). Here, we combine targeted genetic engineering with cardiac subtype-specific differentiation of human induced pluripotent stem cells (hiPSCs) to explore the role of Kv1.5 in atrial hiPSC-cardiomyocytes. CRISPR/Cas9-mediated mutagenesis of integration-free hiPSCs was employed to generate a functional KCNA5 knockout...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28729726/heart-regeneration-and-repair-after-myocardial-infarction-translational-opportunities-for-novel-therapeutics
#5
REVIEW
Thomas J Cahill, Robin P Choudhury, Paul R Riley
Current therapies for heart failure after myocardial infarction are limited and non-curative. Although regenerative approaches are receiving significant attention, clinical efforts that involve transplantation of presumed stem and progenitor cells have largely failed to deliver. Recent studies of endogenous heart regeneration in model organisms, such as zebrafish and neonatal mice, are yielding mechanistic insights into the roles of cardiomyocyte proliferation, resident stem cell niches, neovascularization, the immune system and the extracellular matrix...
July 21, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28727019/triennial-growth-and-development-symposium-dedifferentiated-fat-cells-potential-and-perspectives-for-their-use-in-clinical-and-animal-science-purpose
#6
M S Duarte, R Bueno, W Silva, C F Campos, M P Gionbelli, S E F Guimarães, F F Silva, P S Lopes, G J Hausman, M V Dodson
An increasing body of evidences has demonstrated the ability of the mature adipocyte to dedifferentiate into a population of proliferative-competent cells known as dedifferentiated fat (DFAT) cells. As early as the 1970s, in vitro studies showed that DFAT cells may be obtained by ceiling culture, which takes advantage of the buoyancy property of lipid-filled cells. It was documented that DFAT cells may acquire a phenotype similar to mesenchymal stem cells and yet may differentiate into multiple cell lineages, such as skeletal and smooth muscle cells, cardiomyocytes, osteoblasts, and adipocytes...
May 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28724793/a-bag3-chaperone-complex-maintains-cardiomyocyte-function-during-proteotoxic-stress
#7
Luke M Judge, Juan A Perez-Bermejo, Annie Truong, Alexandre Js Ribeiro, Jennie C Yoo, Christina L Jensen, Mohammad A Mandegar, Nathaniel Huebsch, Robyn M Kaake, Po-Lin So, Deepak Srivastava, Beth L Pruitt, Nevan J Krogan, Bruce R Conklin
Molecular chaperones regulate quality control in the human proteome, pathways that have been implicated in many diseases, including heart failure. Mutations in the BAG3 gene, which encodes a co-chaperone protein, have been associated with heart failure due to both inherited and sporadic dilated cardiomyopathy. Familial BAG3 mutations are autosomal dominant and frequently cause truncation of the coding sequence, suggesting a heterozygous loss-of-function mechanism. However, heterozygous knockout of the murine BAG3 gene did not cause a detectable phenotype...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28724751/tomo-seq-identifies-sox9-as-a-key-regulator-of-cardiac-fibrosis-during-ischemic-injury
#8
Grégory P A Lacraz, Jan Philipp Junker, Monika M Gladka, Bas Molenaar, Koen T Scholman, Marta Vigil-Garcia, Danielle Versteeg, Hesther de Ruiter, Marit W Vermunt, Menno P Creyghton, Manon M H Huibers, Nicolaas de Jonge, Alexander van Oudenaarden, Eva van Rooij
Background -Cardiac ischemic injury induces a pathological remodeling response, which can ultimately lead to heart failure. Detailed mechanistic insights into molecular signaling pathways relevant for different aspects of cardiac remodeling will support the identification of novel therapeutic targets. Methods -While genome-wide transcriptome analysis on diseased tissues has greatly advanced our understanding of the regulatory networks that drive pathological changes in the heart, this approach has been disadvantaged by the fact that the signals are derived from tissue homogenates...
July 19, 2017: Circulation
https://www.readbyqxmd.com/read/28721524/human-ipsc-derived-cardiomyocytes-for-investigation-of-disease-mechanisms-and-therapeutic-strategies-in-inherited-arrhythmia-syndromes-strengths-and-limitations
#9
Simona Casini, Arie O Verkerk, Carol Ann Remme
During the last two decades, significant progress has been made in the identification of genetic defects underlying inherited arrhythmia syndromes, which has provided some clinical benefit through elucidation of gene-specific arrhythmia triggers and treatment. However, for most arrhythmia syndromes, clinical management is hindered by insufficient knowledge of the functional consequences of the mutation in question, the pro-arrhythmic mechanisms involved, and hence the most optimal treatment strategy. Moreover, disease expressivity and sensitivity to therapeutic interventions often varies between mutations and/or patients, underlining the need for more individualized strategies...
July 18, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28718902/pluripotent-stem-cell-based-platforms-in-cardiac-disease-modeling-and-drug-testing
#10
N Shaheen, A Shiti, L Gepstein
The ability to generate patient/disease-specific human pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) brings a unique value to the fields of cardiac disease modeling, drug testing, drug discovery, and precision medicine. Further integration of emerging innovative technologies such as developmental-biology inspired differentiation into chamber-specific cardiomyocyte subtypes, genome-editing, tissue-engineering, and novel functional phenotyping methodologies should facilitate even more advanced investigations...
August 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28718622/graphene-sheet-induced-global-maturation-of-cardiomyocytes-derived-from-human-induced-pluripotent-stem-cells
#11
Jiaxian Wang, Chang Cui, Haiyan Nan, Yuanfang Yu, Yini Xiao, Ellen Poon, Gang Yang, Xijie Wang, Chenchen Wang, Lingsong Li, Kenneth Richard Boheler, Xu Ma, Xin Cheng, Zhenhua Ni, Minglong Chen
Human induced pluripotent stem cells (hiPSCs) can proliferate infinitely. Their ability to differentiate into cardiomyocytes provides abundant sources for disease modeling, drug screening and regenerative medicine. However, hiPSC-derived cardiomyocytes (hiPSC-CMs) display a low degree of maturation and fetal-like properties. Current in vitro differentiation methods do not mimic the structural, mechanical, and physiological properties of the cardiogenesis niche. Recently, we present an efficient cardiac maturation platform that combines hiPSCs monolayer cardiac differentiation with graphene substrate which is a biocompatible and superconductive material...
July 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28717111/usefulness-of-cardiotoxicity-assessment-using-calcium-transient-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#12
Hitoshi Watanabe, Yayoi Honda, Jiro Deguchi, Toru Yamada, Kiyoko Bando
Monitoring dramatic changes in intracellular calcium ion levels during cardiac contraction and relaxation, known as calcium transient, in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) would be an attractive strategy for assessing compounds on cardiac contractility. In addition, as arrhythmogenic compounds are known to induce characteristic waveform changes in hiPSC-CMs, it is expected that calcium transient would allow evaluation of not only compound-induced effects on cardiac contractility, but also compound arrhythmogenic potential...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28715029/anisotropic-microfibrous-scaffolds-enhance-the-organization-and-function-of-cardiomyocytes-derived-from-induced-pluripotent-stem-cells
#13
Maureen Wanjare, Luqia Hou, Karina H Nakayama, Joseph J Kim, Nicholas P Mezak, Oscar J Abilez, Evangeline Tzatzalos, Joseph C Wu, Ngan F Huang
Engineering of myocardial tissue constructs is a promising approach for treatment of coronary heart disease. To engineer myocardial tissues that better mimic the highly ordered physiological arrangement and function of native cardiomyocytes, we generated electrospun microfibrous polycaprolactone scaffolds with either randomly oriented (14 μm fiber diameter) or parallel-aligned (7 μm fiber diameter) microfiber arrangement and co-seeded the scaffolds with human induced pluripotent stem cell-derived cardiomyocytes (iCMs) and endothelial cells (iECs) for up to 12 days after iCM seeding...
July 17, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28713868/21st-century-cardio-oncology-identifying-cardiac-safety-signals-in-the-era-of-personalized-medicine
#14
Calvin Chen Sheng, Laleh Amiri-Kordestani, Todd Palmby, Thomas Force, Charles C Hong, Joseph C Wu, Kevin Croce, Geoffrey Kim, Javid Moslehi
Cardiotoxicity is a well-established complication of oncology therapies. Cardiomyopathy resulting from anthracyclines is a classic example. In the past decade, an explosion of novel cancer therapies, often targeted and more specific than traditional therapies, has revolutionized oncology therapy and dramatically changed cancer prognosis. However, some of these therapies have introduced an assortment of cardiovascular (CV) complications. At times, these devastating outcomes have only become apparent after drug approval and have limited the use of potent therapies...
August 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28711757/cxcr4-and-cxcr7-play-distinct-roles-in-cardiac-lineage-specification-and-pharmacologic-%C3%AE-adrenergic-response
#15
Delaine K Ceholski, Irene C Turnbull, Venu Pothula, Laura Lecce, Andrew A Jarrah, Changwon Kho, Ahyoung Lee, Lahouaria Hadri, Kevin D Costa, Roger J Hajjar, Sima T Tarzami
CXCR4 and CXCR7 are prominent G protein-coupled receptors (GPCRs) for chemokine stromal cell-derived factor-1 (SDF-1/CXCL12). This study demonstrates that CXCR4 and CXCR7 induce differential effects during cardiac lineage differentiation and β-adrenergic response in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Using lentiviral vectors to ablate CXCR4 and/or CXCR7 expression, hiPSC-CMs were tested for phenotypic and functional properties due to gene knockdown. Gene expression and flow cytometry confirmed the pluripotent and cardiomyocyte phenotype of undifferentiated and differentiated hiPSCs, respectively...
July 8, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28710827/comparison-of-non-coding-rnas-in-exosomes-and-functional-efficacy-of-human-embryonic-stem-cell-versus-induced-pluripotent-stem-cell-derived-cardiomyocytes
#16
Won Hee Lee, Wenyi Chen, Ning-Yi Shao, Dan Xiao, Xulei Qin, Natalie Baker, Hye Ryeong Michelle Bae, Praveen Shukla, Haodi Wu, Kazuki Kodo, Sang-Ging Ong, Joseph C Wu
BACKGROUND: Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can serve as unlimited cell sources for cardiac regenerative therapy. However, the functional equivalency between human ESC-CMs and iPSC-CMs for cardiac regenerative therapy has not been demonstrated. Here we performed a head-to-head comparison of ESC-CMs and iPSC-CMs in their ability to restore cardiac function in a rat myocardial infarction (MI) model as well as their exosomal secretome...
July 14, 2017: Stem Cells
https://www.readbyqxmd.com/read/28710467/human-ipsc-derived-cardiomyocytes-cultured-in-3d-engineered-heart-tissue-show-physiological-upstroke-velocity-and-sodium-current-density
#17
Marc D Lemoine, Ingra Mannhardt, Kaja Breckwoldt, Maksymilian Prondzynski, Frederik Flenner, Bärbel Ulmer, Marc N Hirt, Christiane Neuber, András Horváth, Benjamin Kloth, Hermann Reichenspurner, Stephan Willems, Arne Hansen, Thomas Eschenhagen, Torsten Christ
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising tool for drug testing and modelling genetic disorders. Abnormally low upstroke velocity is a current limitation. Here we investigated the use of 3D engineered heart tissue (EHT) as a culture method with greater resemblance to human heart tissue in comparison to standard technique of 2D monolayer (ML) format. INa was measured in ML or EHT using the standard patch-clamp technique. INa density was ~1.8 fold larger in EHT (-18...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28708594/hypoxia-favors-myosin-heavy-chain-beta-gene-expression-in-an-hif-1alpha-dependent-manner
#18
Lucia Binó, Jiřina Procházková, Katarzyna Anna Radaszkiewicz, Jan Kučera, Jana Kudová, Jiří Pacherník, Lukáš Kubala
The potentiation of the naturally limited regenerative capacity of the heart is dependent on an understanding of the mechanisms that are activated in response to pathological conditions such as hypoxia. Under these conditions, the expression of genes suggested to support cardiomyocyte survival and heart adaptation is triggered. Particularly important are changes in the expression of myosin heavy chain (MHC) isoforms. We propose here that alterations in the expression profiles of MHC genes are induced in response to hypoxia and are primarily mediated by hypoxia inducible factor (HIF)...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28706272/modeling-atrial-fibrillation-using-human-embryonic-stem-cell-derived-atrial-tissue
#19
Zachary Laksman, Marianne Wauchop, Eric Lin, Stephanie Protze, Jeehoon Lee, Wallace Yang, Farzad Izaddoustdar, Sanam Shafaattalab, Lior Gepstein, Glen F Tibbits, Gordon Keller, Peter H Backx
Since current experimental models of Atrial Fibrillation (AF) have significant limitations, we used human embryonic stem cells (hESCs) to generate an atrial-specific tissue model of AF for pharmacologic testing. We generated atrial-like cardiomyocytes (CMs) from hESCs which preferentially expressed atrial-specific genes, and had shorter action potential (AP) durations compared to ventricular-like CMs. We then generated confluent atrial-like CM sheets and interrogated them using optical mapping techniques. Atrial-like CM sheets (~1 cm in diameter) showed uniform AP propagation, and rapid re-entrant rotor patterns, as seen in AF could be induced...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28699232/acetylated-stat3-functions-as-molecular-adaptor-independent-of-transcriptional-activity-during-human-cardiogenesis
#20
Ashish Mehta, Chrishan J A Ramachandra, Anuja Chitre, Pritpal Singh, Chong Hui Lua, Winston Shim
Activation of signal transducer and activator of transcription 3 (STAT3) is imperative for mammalian development, specifically cardiogenesis. STAT3 phosphorylation and acetylation are key post-translational modifications that regulate its transcriptional activity. Significance of such modifications during human cardiogenesis remains elusive. Using human pluripotent stem cells (hPSCs) to recapitulate cardiogenesis, two independently modified STAT3α (92kDa) isoforms (phosphorylated and acetylated), which perform divergent functions were identified during cardiomyocyte formation...
July 11, 2017: Stem Cells
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