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Human embryonic stem cells derived cardiomyocytes

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https://www.readbyqxmd.com/read/28925362/generation-of-a-klf15-homozygous-knockout-human-embryonic-stem-cell-line-using-paired-crispr-cas9n-and-human-cardiomyocytes-derivation
#1
Claudia Noack, Luis Peter Haupt, Wolfram-Hubertus Zimmermann, Katrin Streckfuss-Bömeke, Laura Cecilia Zelarayán
Krueppel-like factor 15 (KLF15) is abundantly expressed in liver, kidney, and muscle, including myocardium. In the adult heart KLF15 is important to maintain homeostasis and to repress hypertrophic remodeling. We generated a homozygous hESC KLF15 knockout (KO) line using paired CRISPR/Cas9n. KLF15-KO cells maintained full pluripotency and differentiation potential as well as genomic integrity. We demonstrated that KLF15-KO cells can be differentiated into morphologically normal cardiomyocytes turning them into a valuable tool for studying human KLF15-mediated mechanisms resulting in human cardiac dysfunction...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28878117/tead1-is-required-for-maintaining-adult-cardiomyocyte-function-and-its-loss-results-in-lethal-dilated-cardiomyopathy
#2
Ruya Liu, Jeongkyung Lee, Byung S Kim, Qiongling Wang, Samuel K Buxton, Nikhil Balasubramanyam, Jean J Kim, Jianrong Dong, Aijun Zhang, Shumin Li, Anisha A Gupte, Dale J Hamilton, James F Martin, George G Rodney, Cristian Coarfa, Xander Ht Wehrens, Vijay K Yechoor, Mousumi Moulik
Heart disease remains the leading cause of death worldwide, highlighting a pressing need to identify novel regulators of cardiomyocyte (CM) function that could be therapeutically targeted. The mammalian Hippo/Tead pathway is critical in embryonic cardiac development and perinatal CM proliferation. However, the requirement of Tead1, the transcriptional effector of this pathway, in the adult heart is unknown. Here, we show that tamoxifen-inducible adult CM-specific Tead1 ablation led to lethal acute-onset dilated cardiomyopathy, associated with impairment in excitation-contraction coupling...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28859128/plasma-microvesicle-analysis-identifies-microrna-129-5p-as-a-biomarker-of-heart-failure-in-univentricular-heart-disease
#3
Sweta Ramachandran, Alexander Lowenthal, Carissa Ritner, Shiri Lowenthal, Harold S Bernstein
Biomarkers of heart failure in adults have been extensively studied. However, biomarkers to monitor the progression of heart failure in children with univentricular physiology are less well understood. We proposed that as mediators of diverse pathophysiology, miRNAs contained within circulating microvesicles could serve as biomarkers for the presence and progression of heart failure in univentricular patients. To test this, we studied the association of heart failure with elevations in specific miRNAs isolated from circulating microvesicles in a cohort of children with univentricular heart disease and heart failure...
2017: PloS One
https://www.readbyqxmd.com/read/28795648/human-embryonic-stem-cell-derived-cardiomyocytes-self-arrange-with-areas-of-different-subtypes-during-differentiation
#4
Maj Linea Vestergaard, Søren J Grubb, Karen Koefod Rasmussen, Zoe Anderson-Jenkins, Kristina Grunnet-Lauridsen, Kristine Calloe, Christian Clausen, Søren T Christensen, Kjeld Møllgård, Claus Yding Andersen
The derivation of functional cardiomyocytes (CMs) from human embryonic stem cells (hESC) represents a unique way of studying human cardiogenesis, including the development of CM subtypes. In this study, we investigated the development and organization of CMs derived from hESCs (hESC-CMs) and examined how the expression of CM subtypes correspond to human in vivo cardiogenesis. Beating clusters were used to determine cardiac differentiation, which was evaluated by the expression of cardiac genes GATA4 and TNNT2 and subcellular localization of GATA4 and NKX2...
August 10, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28733255/nanofiber-structured-hydrogel-yarns-with-ph-response-capacity-and-cardiomyocyte-drivability-for-bio-microactuator-application
#5
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/28710827/comparison-of-non-coding-rnas-in-exosomes-and-functional-efficacy-of-human-embryonic-stem-cell-versus-induced-pluripotent-stem-cell-derived-cardiomyocytes
#6
Won Hee Lee, Wen-Yi Chen, Ning-Yi Shao, Dan Xiao, Xulei Qin, Natalie Baker, Hye Ryeong Bae, Tzu-Tang Wei, Yongjun Wang, Praveen Shukla, Haodi Wu, Kazuki Kodo, Sang-Ging Ong, Joseph C Wu
Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived CMs (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/28706272/modeling-atrial-fibrillation-using-human-embryonic-stem-cell-derived-atrial-tissue
#7
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/28663367/genome-wide-temporal-profiling-of-transcriptome-and-open-chromatin-of-early-cardiomyocyte-differentiation-derived-from-hipscs-and-hescs
#8
Qing Liu, Chao Jiang, Jin Xu, Ming-Tao Zhao, Kevin Van Bortle, Xun Cheng, Guangwen Wang, Howard Y Chang, Joseph C Wu, Michael P Snyder
RATIONALE: Recent advances have improved our ability to generate cardiomyocytes from human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs). However, our understanding of the transcriptional regulatory networks underlying early stages (ie, from mesoderm to cardiac mesoderm) of cardiomyocyte differentiation remains limited. OBJECTIVE: To characterize transcriptome and chromatin accessibility during early cardiomyocyte differentiation from hiPSCs and hESCs...
August 4, 2017: Circulation Research
https://www.readbyqxmd.com/read/28637969/development-of-a-patient-derived-induced-pluripotent-stem-cell-model-for-the-investigation-of-scn5a-d1275n-related-cardiac-sodium-channelopathy
#9
Mamoru Hayano, Takeru Makiyama, Tsukasa Kamakura, Hiroshi Watanabe, Kenichi Sasaki, Shunsuke Funakoshi, Yimin Wuriyanghai, Suguru Nishiuchi, Takeshi Harita, Yuta Yamamoto, Hirohiko Kohjitani, Sayako Hirose, Fumika Yokoi, Jiarong Chen, Osamu Baba, Takahiro Horie, Kazuhisa Chonabayashi, Seiko Ohno, Futoshi Toyoda, Yoshinori Yoshida, Koh Ono, Minoru Horie, Takeshi Kimura
BACKGROUND: TheSCN5Agene encodes the α subunit of the cardiac voltage-gated sodium channel, NaV1.5. The missense mutation, D1275N, has been associated with a range of unusual phenotypes associated with reduced NaV1.5 function, including cardiac conduction disease and dilated cardiomyopathy. Curiously, the reported biophysical properties ofSCN5A-D1275N channels vary with experimental system.Methods and Results:First, using a human embryonic kidney (HEK) 293 cell-based heterologous expression system, theSCN5A-D1275N channels showed similar maximum sodium conductance but a significantly depolarizing shift of activation gate (+10 mV) compared to wild type...
June 20, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28570546/electrophysiological-analysis-of-human-pluripotent-stem-cell-derived-cardiomyocytes-hpsc-cms-using-multi-electrode-arrays-meas
#10
Luca Sala, Dorien Ward-van Oostwaard, Leon G J Tertoolen, Christine L Mummery, Milena Bellin
Cardiomyocytes can now be derived with high efficiency from both human embryonic and human induced-Pluripotent Stem Cells (hPSC). hPSC-derived cardiomyocytes (hPSC-CMs) are increasingly recognized as having great value for modeling cardiovascular diseases in humans, especially arrhythmia syndromes. They have also demonstrated relevance as in vitro systems for predicting drug responses, which makes them potentially useful for drug-screening and discovery, safety pharmacology and perhaps eventually for personalized medicine...
May 12, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28550304/electronic-supplementary-materialidentification-of-a-na-k-atpase-inhibition-independent-proarrhythmic-ionic-mechanisms-of-cardiac-glycosides
#11
Cai Hong Koh, Jianjun Wu, Ying Ying Chung, Zhenfeng Liu, Rong-Rong Zhang, Ketpin Chong, Vladimir Korzh, Sherwin Ting, Steve Oh, Winston Shim, Hai-Yan Tian, Heming Wei
The current study explored the Na(+)/K(+)-ATPase (NKA) inhibition-independent proarrhythmic mechanisms of cardiac glycosides (CGs) which are well-known NKA inhibitors. With the cytosolic Ca(2+) chelated by EGTA and BAPTA or extracellular Ca(2+) replaced by Ba(2+), effects of bufadienolides (bufalin (BF) and cinobufagin (CBG)) and cardenolides (ouabain (Oua) and pecilocerin A (PEA)) on the L-type calcium current (I Ca,L) were recorded in heterologous expression Cav1.2-CHO cells and human embryonic stem cell-derived cardiomyocytes (hESC-CMs)...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28543763/7-8-3-trihydroxyflavone-protects-h-r-induced-apoptosis-and-induces-in-vivo-growth-of-human-embryonic-stem-cell-derived-cardiomyocytes
#12
Jiaxiang Li, Cuiping Wang, Bao Zhang Baiyun Tang
BACKGROUND: Cellular therapy of human embryonic stem cell-derived cardiomyocytes (hES-CMs) holds great promise for regenerating infarcted cardiac tissues. Yet, the major challenge remains as little cells survived after grafting. In this study, we examined whether treating hES-CMs with 7, 8, 3'-Trihydroxyflavone (THF) may improve hES-CMs developments both in vitro and in vivo. METHOD: HES-CMs were differentiated in vitro, and treated with 5 μ59M THF for 24 h...
May 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28536247/circadian-networks-in-human-embryonic-stem-cell-derived-cardiomyocytes
#13
Pieterjan Dierickx, Marit W Vermunt, Mauro J Muraro, Menno P Creyghton, Pieter A Doevendans, Alexander van Oudenaarden, Niels Geijsen, Linda W Van Laake
Cell-autonomous circadian oscillations strongly influence tissue physiology and pathophysiology of peripheral organs including the heart, in which the circadian clock is known to determine cardiac metabolism and the outcome of for instance ischemic stress. Human pluripotent stem cells represent a powerful tool to study developmental processes in vitro, but the extent to which human embryonic stem (ES) cell-derived cardiomyocytes establish circadian rhythmicity in the absence of a systemic context is unknown...
July 2017: EMBO Reports
https://www.readbyqxmd.com/read/28528699/steps-toward-maturation-of-embryonic-stem-cell-derived-cardiomyocytes-by-defined-physical-signals
#14
Nian Shen, Anne Knopf, Claas Westendorf, Udo Kraushaar, Julia Riedl, Hannah Bauer, Simone Pöschel, Shannon Lee Layland, Monika Holeiter, Stefan Knolle, Eva Brauchle, Ali Nsair, Svenja Hinderer, Katja Schenke-Layland
Cardiovascular disease remains a leading cause of mortality and morbidity worldwide. Embryonic stem cell-derived cardiomyocytes (ESC-CMs) may offer significant advances in creating in vitro cardiac tissues for disease modeling, drug testing, and elucidating developmental processes; however, the induction of ESCs to a more adult-like CM phenotype remains challenging. In this study, we developed a bioreactor system to employ pulsatile flow (1.48 mL/min), cyclic strain (5%), and extended culture time to improve the maturation of murine and human ESC-CMs...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28524367/transplantation-of-human-villous-trophoblasts-preserves-cardiac-function-in-mice-with-acute-myocardial-infarction
#15
Zegen Wang, Ningzheng Dong, Yayan Niu, Zhiwei Zhang, Ce Zhang, Meng Liu, Tiantian Zhou, Qingyu Wu, Ke Cheng
Over the past decade, cell therapies have provided promising strategies for the treatment of ischaemic cardiomyopathy. Particularly, the beneficial effects of stem cells, including bone marrow stem cells (BMSCs), endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), have been demonstrated by substantial preclinical and clinical studies. Nevertheless stem cell therapy is not always safe and effective. Hence, there is an urgent need for alternative sources of cells to promote cardiac regeneration...
May 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28482139/contributions-of-bmps-in-cardiac-repair-cells-in-3d-in-vitro-models-and-angiogenesis
#16
Isabella Pallotta, Bruce Sun, Gregory Lallos, Cecile Terrenoire, Donald O Freytes
One of the main efforts in myocardial tissue engineering consists of designing cardiac tissues able to rescue the reduction in heart function once implanted at the site of myocardial infarction. To date, the efficiency of this approach in pre-clinical applications is limited in part by our incomplete understanding of the inflammatory environment known to be present at the site of myocardial infarct and by poor vascularization. We recently reported that polarized macrophages known to be present at the site of myocardial infarction secrete BMP-2 and BMP-4 proteins causing changes in the expression of cardiac proteins in a 2D in vitro model...
May 8, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28333933/geometry-dependent-functional-changes-in-ipsc-derived-cardiomyocytes-probed-by-functional-imaging-and-rna-sequencing
#17
Christopher A Werley, Miao-Ping Chien, Jellert Gaublomme, Karthik Shekhar, Vincent Butty, B Alexander Yi, Joel M Kralj, William Bloxham, Laurie A Boyer, Aviv Regev, Adam E Cohen
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising platform for cardiac studies in vitro, and possibly for tissue repair in humans. However, hiPSC-CM cells tend to retain morphology, metabolism, patterns of gene expression, and electrophysiology similar to that of embryonic cardiomyocytes. We grew hiPSC-CM in patterned islands of different sizes and shapes, and measured the effect of island geometry on action potential waveform and calcium dynamics using optical recordings of voltage and calcium from 970 islands of different sizes...
2017: PloS One
https://www.readbyqxmd.com/read/28320859/2-arachidonoylglycerol-ameliorates-inflammatory-stress-induced-insulin-resistance-in-cardiomyocytes
#18
Dipanjan Chanda, Yvonne Oligschlaeger, Ilvy Geraets, Yilin Liu, Xiaoqing Zhu, Jieyi Li, Miranda Nabben, Will Coumans, Joost J F P Luiken, Jan F C Glatz, Dietbert Neumann
Several studies have linked impaired glucose uptake and insulin resistance (IR) to functional impairment of the heart. Recently, endocannabinoids have been implicated in cardiovascular disease. However, the mechanisms involving endocannabinoid signaling, glucose uptake, and IR in cardiomyocytes are understudied. Here we report that the endocannabinoid 2-arachidonoylglycerol (2-AG), via stimulation of cannabinoid type 1 (CB1) receptor and Ca(2+)/calmodulin-dependent protein kinase β, activates AMP-activated kinase (AMPK), leading to increased glucose uptake...
April 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28288859/mitochondrial-toxicity-of-perfluorooctane-sulfonate-in-mouse-embryonic-stem-cell-derived-cardiomyocytes
#19
Lei-Lei Tang, Jia-Dan Wang, Ting-Ting Xu, Zhe Zhao, Jia-Jie Zheng, Ren-Shan Ge, Dan-Yan Zhu
Perfluorooctane sulfonate (PFOS) is a persistent organic contaminant that may cause cardiotoxicity in animals and humans. However, little is known about the underlying mechanism by which it affects the organelle toxicity in cardiomyocytes during the cardiogenesis. Our previous proteomic study showed that differences of protein expression mainly existed in mitochondria of cardiomyocytes differentiated from embryonic stem (ES) cells after exposure to PFOS. Here, we focused on mitochondrial toxicity of PFOS in ES cell-derived cardiomyocytes...
May 1, 2017: Toxicology
https://www.readbyqxmd.com/read/28279214/cardiotoxicity-evaluation-using-human-embryonic-stem-cells-and-induced-pluripotent-stem-cell-derived-cardiomyocytes
#20
Qi Zhao, Xijie Wang, Shuyan Wang, Zheng Song, Jiaxian Wang, Jing Ma
BACKGROUND: Cardiotoxicity remains an important concern in drug discovery. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have become an attractive platform to evaluate cardiotoxicity. However, the consistency between human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in prediction of cardiotoxicity has yet to be elucidated. METHODS: Here we screened the toxicities of four representative drugs (E-4031, isoprenaline, quinidine, and haloperidol) using both hESC-CMs and hiPSC-CMs, combined with an impedance-based bioanalytical method...
March 9, 2017: Stem Cell Research & Therapy
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