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Cardiomyocyte stem cells

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https://www.readbyqxmd.com/read/29777691/improving-electrical-properties-of-ipsc-cardiomyocytes-by-enhancing-cx43-expression
#1
Valentin Sottas, Carl-Mattheis Wahl, Mihnea C Trache, Michael Bartolf-Kopp, Sidney Cambridge, Markus Hecker, Nina D Ullrich
The therapeutic potential of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is limited by immature functional features including low impulse propagation and reduced cell excitability. Key players regulating electrical activity are voltage-gated Na+ channels (Nav 1.5) and gap junctions built from connexin-43 (Cx43). Here we tested the hypothesis that enhanced Cx43 expression increases intercellular coupling and influences excitability by modulating Nav 1.5. Using transgenic approaches, Cx43 and Nav 1...
May 16, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29776438/uninterrupted-monitoring-of-drug-effects-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-with-bioluminescence-ca-2-microscopy
#2
Kazushi Suzuki, Takahito Onishi, Chieko Nakada, Shunsuke Takei, Matthew J Daniels, Masahiro Nakano, Tomoki Matsuda, Takeharu Nagai
OBJECTIVE: Cardiomyocytes derived from human-induced pluripotent stem cells are a powerful platform for high-throughput drug screening in vitro. However, current modalities for drug testing, such as electrophysiology and fluorescence imaging have inherent drawbacks. To circumvent these problems, we report the development of a bioluminescent Ca2+ indicator GmNL(Ca2+ ), and its application in a customized microscope for high-throughput drug screening. RESULTS: GmNL(Ca2+ ) gives a 140% signal change with Ca2+ , and can image drug-induced changes of Ca2+ dynamics in cultured cells...
May 18, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29774393/developmental-origin-of-the-cardiac-conduction-system-insight-from-lineage-tracing
#3
Rajiv A Mohan, Bastiaan J Boukens, Vincent M Christoffels
The components of the cardiac conduction system (CCS) generate and propagate the electrical impulse that initiates cardiac contraction. These interconnected components share properties, such as automaticity, that set them apart from the working myocardium of the atria and ventricles. A variety of tools and approaches have been used to define the CCS lineages. These include genetic labeling of cells expressing lineage markers and fate mapping of dye labeled cells, which we will discuss in this review. We conclude that there is not a single CCS lineage, but instead early cell fate decisions segregate the lineages of the CCS components while they remain interconnected...
May 17, 2018: Pediatric Cardiology
https://www.readbyqxmd.com/read/29774076/the-human-somatostatin-receptor-type-2-as-an-imaging-and-suicide-reporter-gene-for-pluripotent-stem-cell-derived-therapy-of-myocardial-infarction
#4
Katrien Neyrinck, Natacha Breuls, Bryan Holvoet, Wouter Oosterlinck, Esther Wolfs, Hubert Vanbilloen, Olivier Gheysens, Robin Duelen, Willy Gsell, Ivo Lambrichts, Uwe Himmelreich, Catherine M Verfaillie, Maurilio Sampaolesi, Christophe M Deroose
Rationale: Pluripotent stem cells (PSCs) are being investigated as a cell source for regenerative medicine since they provide an infinitive pool of cells that are able to differentiate towards every cell type of the body. One possible therapeutic application involves the use of these cells to treat myocardial infarction (MI), a condition where billions of cardiomyocytes (CMs) are lost. Although several protocols have been developed to differentiate PSCs towards CMs, none of these provide a completely pure population, thereby still posing a risk for neoplastic teratoma formation...
2018: Theranostics
https://www.readbyqxmd.com/read/29773058/non-cardiomyocytes-in-heart-regeneration
#5
Jie Feng, Yandong Li, Yu Nie
Heart failure represents a challenging clinical and public health problem and is associated with significant morbidity and mortality. Mechanistically, loss of cardiomyocytes leads to decompensated ventricular remodeling, which eventually progressed to cardiac failure. Regenerative medicine aimed to supplement functional cardiomyocytes is supposedly a promising approach for the effective treatment of heart failure. Over the past decades, investigations on heart regeneration have revealed the regulating networks of cardiomyocyte proliferation...
May 17, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29772700/inhibition-of-arachidonate-12-15-lipoxygenase-improves-%C3%AE-galactosidase-efficacy-in-ipsc-derived-cardiomyocytes-from-fabry-patients
#6
Yueh Chien, Shih-Jie Chou, Yuh-Lih Chang, Hsin-Bang Leu, Yi-Ping Yang, Ping-Hsing Tsai, Ying-Hsiu Lai, Kuan-Hsuan Chen, Wei-Chao Chang, Shih-Hsien Sung, Wen-Chung Yu
(1) Background: A high incidence of intervening sequence (IVS)4+919 G>A mutation with later-onset cardiac phenotype have been reported in a majority of Taiwan Fabry cohorts. Some evidence indicated that conventional biomarkers failed to predict the long-term progression and therapeutic outcome; (2) Methods: In this study, we constructed an induced pluripotent stem cell (iPSC)-based platform from Fabry cardiomyopathy (FC) patients carrying IVS4+919 G>A mutation to screen for potential targets that may help the conventional treatment; (3) Results: The FC-patient-derived iPSC-differentiated cardiomyocytes (FC-iPSC-CMs) carried an expected IVS4+919 G>A genetic mutation and recapitulated several FC characteristics, including low α-galactosidase A enzyme activity and cellular hypertrophy...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29767235/inhibition-of-microrna%C3%A2-16-protects-mesenchymal-stem-cells-against-apoptosis
#7
Jiang Rui, Shaohong Fang, Yongchen Wang, Bo Lv, Bo Yu, Shufeng Li
Bone marrow‑derived mesenchymal stem cells (BM‑MSCs) have been used in experimental research and clinical trials for heart function restoration and cardiomyocyte regeneration. However, due to a hostile microenvironment created by ischemia, hypoxia and pro‑inflammatory factors, the survival rate of implanted BM‑MSCs remains low. Therefore, strategies that can promote BM‑MSC survival and prevent apoptosis are required. Previous studies have reported that microRNA‑16 (miR‑16) can inhibit cell proliferation by targeting several proteins and signal pathway, not only by inducing apoptosis...
May 11, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29760739/antiarrhythmic-effects-of-carvedilol-and-flecainide-in-cardiomyocytes-derived-from-catecholaminergic-polymorphic-ventricular-tachycardia-patients
#8
R P Pölönen, K Penttinen, H Swan, K Aalto-Setälä
Mutations in the cardiac ryanodine receptor (RYR2) are the leading cause for catecholaminergic polymorphic ventricular tachycardia (CPVT). In this study, we evaluated antiarrhythmic efficacy of carvedilol and flecainide in CPVT patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) carrying different mutations in RYR2. iPSC-CMs were generated from skin biopsies of CPVT patients carrying exon 3 deletion and L4115 or V4653F mutation in RYR2 and of a healthy individual. Ca2+ kinetics and drug effects were studied with Fluo-4 AM indicator...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29758359/probing-flecainide-block-of-i-na-using-human-pluripotent-stem-cell-derived-ventricular-cardiomyocytes-adapted-to-automated-patch-clamping-and-2d-monolayers
#9
Lin Geng, Chi-Wing Kong, Andy O T Won, Angie Man-Yee Shum, Maggie Z Y Chow, Hui Che, Chenzi Zhang, Ka-Long Yau, Camie W Chan, Wendy Keung, Ronald A Li
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are emerging tools for applications such as drug discovery and screening for pro-arrhythmogenicity and cardiotoxicity as leading causes for drug attrition. Understanding the electrophysiology (EP) of hPSC-CMs is essential but conventional manual patch-clamping is highly laborious and low-throughput. Here we adapted hPSC-CMs derived from two human embryonic stem cell (hESC) lines, HES2 and H7, for a 16-channel automated planar-recording approach for single-cell EP characterization...
May 11, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29758225/trpv6-protects-er-stress-induced-apoptosis-via-atf6%C3%AE-trpv6-jnk-pathway-in-human-embryonic-stem-cell-derived-cardiomyocytes
#10
Zhichao Li, Zhaoyue Meng, Jun Lu, Francis M Chen, Wing-Tak Wong, Gary Tse, Changbo Zheng, Wendy Keung, Kennis Tse, Ronald A Li, Liwen Jiang, Xiaoqiang Yao
Human pluripotent stem cell-derived cardiomyocytes have potential applications in disease modeling and drug screening. Therefore, it is important to understand the mechanisms and signaling pathways underlying the survival and death of these cells. Endoplasmic reticulum (ER) stress is triggered by various cellular stresses that disturb protein folding in the ER. Cells cope with ER stress by activating the unfolded protein response (UPR), a homeostatic signaling network that orchestrates the recovery of ER function...
May 11, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29755568/exosomes-secreted-by-normoxic-and-hypoxic-cardiosphere-derived-cells-have-anti-apoptotic-effect
#11
Helia Namazi, Iman Namazi, Parisa Ghiasi, Hassan Ansari, Sarah Rajabi, Ensiyeh Hajizadeh-Saffar, Nasser Aghdami, Elham Mohit
Cardiosphere-derived cells (CDCs) have emerged as one of the most promising stem cell types for cardiac protection and repair. Exosomes are required for the regenerative effects of human CDCs and mimic the cardioprotective benefits of CDCs such as anti-apoptotic effect in animal myocardial infarction (MI) models. Here we aimed to investigate the anti-apoptotic effect of the hypoxic and normoxic human CDCs-derived exosomes on induced apoptosis in human embryonic stem cell-derived cardiomyocytes (hESC-CMs). In this study, CDCs were cultured under normoxic (18% O2 ) and hypoxic (1% O2 ) conditions and CDC-exosomes were isolated from conditioned media by differential ultracentrifugation...
2018: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/29754959/human-induced-pluripotent-stem-cell-derived-cardiac-cell-sheets-expressing-genetically-encoded-voltage-indicator-for-pharmacological-and-arrhythmia-studies
#12
Naim Shaheen, Assad Shiti, Irit Huber, Rami Shinnawi, Gil Arbel, Amira Gepstein, Noga Setter, Idit Goldfracht, Amit Gruber, Snizhanna V Chorna, Lior Gepstein
Fulfilling the potential of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes for studying conduction and arrhythmogenesis requires development of multicellular models and methods for long-term repeated tissue phenotyping. We generated confluent hiPSC-derived cardiac cell sheets (hiPSC-CCSs), expressing the genetically encoded voltage indicator ArcLight. ArcLight-based optical mapping allowed generation of activation and action-potential duration (APD) maps, which were validated by mapping the same hiPSC-CCSs with the voltage-sensitive dye, Di-4-ANBDQBS...
May 7, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29754170/cardiac-support-device-asd-delivers-bone-marrow-stem-cells-repetitively-to-epicardium-has-promising-curative-effects-in-advanced-heart-failure
#13
Shizhong Yue, Muhammad Naveed, Wang Gang, Dingding Chen, Zhijie Wang, Feng Yu, Xiaohui Zhou
Ventricular restraint therapy is a non-transplant surgical option for the management of advanced heart failure (HF). To augment the therapeutic applications, it is hypothesized that ASD shows remarkable capabilities not only in delivering stem cells but also in dilated ventricles. Male SD rats were divided into four groups (n = 6): normal, HF, HF + ASD, and HF + ASD-BMSCs respectively. HF was developed by left anterior descending (LAD) coronary artery ligation in all groups except normal group. Post-infarcted electrocardiography (ECG) and brain natriuretic peptide (BNP) showed abnormal heart function in all model groups and HF + ASD-BMSCs group showed significant improvement as compared to other HF, HF + ASD groups on day 30...
May 12, 2018: Biomedical Microdevices
https://www.readbyqxmd.com/read/29752948/functional-and-transcriptomic-insights-into-pathogenesis-of-r9c-phospholamban-mutation-using-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#14
Delaine K Ceholski, Irene C Turnbull, Chi-Wing Kong, Simon Koplev, Joshua Mayourian, Przemek A Gorski, Francesca Stillitano, Angelos A Skodras, Mathieu Nonnenmacher, Ninette Cohen, Johan L M Björkegren, Daniel R Stroik, Razvan L Cornea, David D Thomas, Ronald A Li, Kevin D Costa, Roger J Hajjar
Dilated cardiomyopathy (DCM) can be caused by mutations in the cardiac protein phospholamban (PLN). We used CRISPR/Cas9 to insert the R9C PLN mutation at its endogenous locus into a human induced pluripotent stem cell (hiPSC) line from an individual with no cardiovascular disease. R9C PLN hiPSC-CMs display a blunted β-agonist response and defective calcium handling. In 3D human engineered cardiac tissues (hECTs), a blunted lusitropic response to β-adrenergic stimulation was observed with R9C PLN. hiPSC-CMs harboring the R9C PLN mutation showed activation of a hypertrophic phenotype, as evidenced by expression of hypertrophic markers and increased cell size and capacitance of cardiomyocytes...
May 9, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29752300/intramyocardial-angiogenetic-stem-cells-and-epicardial-erythropoietin-save-the-acute-ischemic-heart
#15
Christian Klopsch, Anna Skorska, Marion Ludwig, Heiko Lemcke, Gabriela Maass, Ralf Gaebel, Martin Beyer, Cornelia Lux, Anita Toelk, Karina Müller, Christian Maschmeier, Sarah Rohde, Petra Mela, Brigitte Müller-Hilke, Stefan Jockenhoevel, Brigitte Vollmar, Robert Jaster, Robert David, Gustav Steinhoff
Ischemic heart failure still displays the highest mortality. An early boost of intracardiac regenerative key mechanisms and angiogenetic niche signaling in cardiac mesenchymal stem cells (MSCs) could improve myocardial infarction (MI) healing. Epicardial erythropoietin (EPO, 300U kg-1 ) was compared with intraperitoneal and intramyocardial EPO treatments after acute MI in rats (n=156). Real-time PCR and confocal microscopy revealed epicardial EPO treatment enhanced intracardiac regenerative key indicators (SDF-1, CXCR-4, CD34, Bcl-2, Cyclin D1, Cdc2, MMP2), induced TGF-β/WNT signaling in intramyocardial MSC niches through direct activation of AKT, upregulations of upstream signals FOS and Fzd7 and augmented intracardiac mesenchymal proliferation 24 hours after MI...
May 10, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29751595/optical-electrophysiology-in-the-developing-heart
#16
REVIEW
Kandace Thomas, Julie Goudy, Trevor Henley, Michael Bressan
The heart is the first organ system to form in the embryo. Over the course of development, cardiomyocytes with differing morphogenetic, molecular, and physiological characteristics are specified and differentiate and integrate with one another to assemble a coordinated electromechanical pumping system that can function independently of any external stimulus. As congenital malformation of the heart presents the leading class of birth defects seen in humans, the molecular genetics of heart development have garnered much attention over the last half century...
May 11, 2018: Journal of Cardiovascular Development and Disease
https://www.readbyqxmd.com/read/29751502/the-development-of-compartmentation-of-camp-signaling-in-cardiomyocytes-the-role-of-t-tubules-and-caveolae-microdomains
#17
REVIEW
Navneet K Bhogal, Alveera Hasan, Julia Gorelik
3′-5′-cyclic adenosine monophosphate (cAMP) is a signaling messenger produced in response to the stimulation of cellular receptors, and has a myriad of functional applications depending on the cell type. In the heart, cAMP is responsible for regulating the contraction rate and force; however, cAMP is also involved in multiple other functions. Compartmentation of cAMP production may explain the specificity of signaling following a stimulus. In particular, transverse tubules (T-tubules) and caveolae have been found to be critical structural components for the spatial confinement of cAMP in cardiomyocytes, as exemplified by beta-adrenergic receptor (β-ARs) signaling...
May 3, 2018: Journal of Cardiovascular Development and Disease
https://www.readbyqxmd.com/read/29748973/afm-nano-mechanical-study-of-the-beating-profile-of-hipsc-derived-cardiomyocytes-beating-bodies-wt-and-dm1
#18
S Dinarelli, M Girasole, P Spitalieri, R V Talarico, M Murdocca, A Botta, G Novelli, R Mango, F Sangiuolo, G Longo
Myotonic Dystrophy type 1 (DM1) is the most common form of muscular dystrophy in adults, characterized by a variety of multisystemic features and associated with cardiac anomalies. Among cardiac phenomena, conduction defects, ventricular arrhythmias, and dilated cardiomyopathy represent the main cause of sudden death in DM1 patients. Patient-specific induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent a powerful in vitro model for molecular, biochemical, and physiological studies of disease in the target cells...
May 10, 2018: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/29747586/selective-modulation-of-local-linkages-between-active-transcription-and-oxidative-demethylation-activity-shapes-cardiomyocyte-specific-gene-body-epigenetic-status-in-mice
#19
Mayumi Oda, Shunichi Wakabayashi, N Ari Wijetunga, Shinsuke Yuasa, Hirokazu Enomoto, Ruri Kaneda, Sung Han Yoon, Nishant Mittal, Qiang Jing, Masako Suzuki, John M Greally, Keiichi Fukuda, Shinji Makino
BACKGROUND: Cell-type-specific genes exhibit heterogeneity in genomic contexts and may be subject to different epigenetic regulations through different gene transcriptional processes depending on the cell type involved. The gene-body regions (GBRs) of some cardiomyocyte (CM)-specific genes are long and highly hypomethylated in CMs. To explore the cell-type specificities of epigenetic patterns and functions, multiple epigenetic modifications of GBRs were compared among CMs, liver cells and embryonic stem cells (ESCs)...
May 10, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29745340/problems-in-stem-cell-therapy-for-cardiac-repair-and-tissue-engineering-approaches-based-on-graphene-and-its-derivatives
#20
Ayca Aslan, Adil Allahverdiyev, Melahat Bagirova, Emrah Abamor
BACKGROUND: Today, coronary artery disease is still one of the most important causes of mortality despite advanced surgical methods, pharmacotherapies and organ transplantation. These treatment modalities are intended to prevent further progression of myocardial infarction and do not involve the repair of the damaged part. Therefore, stem cell therapy has emerged as a new approach for the treatment of coronary artery disease. However, there are some restrictions that limit the use of these cells for desired repair...
May 9, 2018: Current Stem Cell Research & Therapy
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