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Human embryonic stem cells derived cardiomyocytes

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https://www.readbyqxmd.com/read/29133340/effects-of-hawthorn-crataegus-pentagyna-leaf-extract-on-electrophysiologic-properties-of-cardiomyocytes-derived-from-human-cardiac-arrhythmia-specific-induced-pluripotent-stem-cells
#1
Sara Pahlavan, Marziyeh Shalchi Tousi, Mahdi Ayyari, Abolfazl Alirezalu, Hassan Ansari, Tomo Saric, Hossein Baharvand
Cardiac arrhythmias are major life-threatening conditions. The landmark discovery of induced pluripotent stem cells has provided a promising in vitro system for modeling hereditary cardiac arrhythmias as well as drug development and toxicity testing. Nowadays, nutraceuticals are frequently used as supplements for cardiovascular therapy. Here we studied the cardiac effects of hawthorn (Crataegus pentagyna) leaf extract using cardiomyocytes (CMs) differentiated from healthy human embryonic stem cells, long QT syndrome type 2 (LQTS2), and catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) patient-specific induced pluripotent stem cells...
November 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29127860/human-embryonic-stem-cell-derived-cardiovascular-progenitor-cells-efficiently-colonize-in-bfgf-tethered-natural-matrix-to-construct-contracting-humanized-rat-hearts
#2
Sarah Rajabi, Sara Pahlavan, Mohammad Kazemi Ashtiani, Hassan Ansari, Saeed Abbasalizadeh, Forough Azam Sayahpour, Fahimeh Varzideh, Sawa Kostin, Nasser Aghdami, Thomas Braun, Hossein Baharvand
Bioengineering of whole hearts using human embryonic stem cells (hESCs)-derived cardiovascular progenitor cells (CPCs) and natural matrices is a promising approach to overcome organ donor shortage threatening millions of patients awaiting for heart transplantation. Here, we developed a novel strategy for generation of heart constructs by repopulating engineered decellularized rat hearts using hESCs-derived CPCs. Careful expansion of CPCs in a scalable stirred-suspension bioreactor combined with step-wise seeding (60 million cells in 3 steps of 20 million per 1...
November 1, 2017: Biomaterials
https://www.readbyqxmd.com/read/29062050/functional-expression-and-pharmaceutical-efficacy-of-cardiac-specific-ion-channels-in-human-embryonic-stem-cell-derived-cardiomyocytes
#3
Han Sol Kim, Jung Won Yoon, Hongliang Li, Geun Ok Jeong, Jin Ju Park, Sung Eun Shin, Il Ho Jang, Jae Ho Kim, Won Sun Park
Cardiomyocytes differentiated from human pluripotent stem cells provide promising tools for screening of cardiotoxic drugs. For evaluation of human pluripotent stem cell-derived cardiomyocytes for cardiotoxicity test, in the present study, human embryonic stem cells (hESCs) were differentiated to cardiomyocytes, followed by metabolic selection to enrich the differentiated cardiomyocytes. The highly purified hESC-derived cardiomyocytes (hESC-CMs) expressed several cardiomyocyte-specific markers including cTnT, MLC2a, and α-SA, but not pluripotency markers, such as OCT4 and NANOG...
October 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29026152/genetic-and-epigenetic-profiling-reveals-ezh2-mediated-down-regulation-of-oct-4-involves-nr2f2-during-cardiac-differentiation-of-human-embryonic-stem-cells
#4
Varsha Pursani, Prasad Pethe, Mohsin Bashir, Prabha Sampath, Vivek Tanavde, Deepa Bhartiya
Human embryonic (hES) stem cells are widely used as an in vitro model to understand global genetic and epigenetic changes that occur during early embryonic development. In-house derived hES cells (KIND1) were subjected to directed differentiation into cardiovascular progenitors (D12) and beating cardiomyocytes (D20). Transcriptome profiling of undifferentiated (D0) and differentiated (D12 and 20) cells was undertaken by microarray analysis. ChIP and sequential ChIP were employed to study role of transcription factor NR2F2 during hES cells differentiation...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29026098/hla-and-histo-blood-group-antigen-expression-in-human-pluripotent-stem-cells-and-their-derivatives
#5
Karin Säljö, Angela Barone, Johan Mölne, Lennart Rydberg, Susann Teneberg, Michael E Breimer
One prerequisite for a successful clinical outcome of human pluripotent stem cell (hPSC) based therapies is immune compatibility between grafted cells/tissue and recipient. This study explores immune determinants of human embryonic stem cell lines (hESC) and induced human pluripotent stem cell (hiPSC) lines and hepatocyte- and cardiomyocyte-like cells derived from these cells. HLA class I was expressed on all pluripotent hPSC lines which upon differentiation into hepatocyte-like cells was considerably reduced in contrast to cardiomyocyte-like cells which retained class I antigens...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29021306/characterization-of-a-human-induced-pluripotent-stem-cell-derived-cardiomyocyte-model-for-the-study-of-variant-pathogenicity-validation-of-a-kcnj2-mutation
#6
Roselle Gélinas, Nabil El Khoury, Marie-A Chaix, Claudine Beauchamp, Azadeh Alikashani, Nathalie Ethier, Gabrielle Boucher, Louis Villeneuve, Laura Robb, Frédéric Latour, Blandine Mondesert, Lena Rivard, Philippe Goyette, Mario Talajic, Céline Fiset, John David Rioux
BACKGROUND: Long-QT syndrome is a potentially fatal condition for which 30% of patients are without a genetically confirmed diagnosis. Rapid identification of causal mutations is thus a priority to avoid at-risk situations that can lead to fatal cardiac events. Massively parallel sequencing technologies are useful for the identification of sequence variants; however, electrophysiological testing of newly identified variants is crucial to demonstrate causality. Long-QT syndrome could, therefore, benefit from having a standardized platform for functional characterization of candidate variants in the physiological context of human cardiomyocytes...
October 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28974514/diminished-prrx1-expression-is-associated-with-increased-risk-of-atrial-fibrillation-and-shortening-of-the-cardiac-action-potential
#7
Nathan R Tucker, Elena V Dolmatova, Honghuang Lin, Rebecca R Cooper, Jiangchuan Ye, William J Hucker, Heather S Jameson, Victoria A Parsons, Lu-Chen Weng, Robert W Mills, Moritz F Sinner, Maxim Imakaev, Jordan Leyton-Mange, Gus Vlahakes, Emelia J Benjamin, Kathryn L Lunetta, Steven A Lubitz, Leonid Mirny, David J Milan, Patrick T Ellinor
BACKGROUND: Atrial fibrillation (AF) affects over 33 million individuals worldwide. Genome-wide association studies have identified at least 30 AF loci, but the mechanisms through which individual variants lead to altered disease risk have remained unclear for the majority of these loci. At the 1q24 locus, we hypothesized that the transcription factor PRRX1 could be a strong candidate gene as it is expressed in the pulmonary veins, a source of AF in many individuals. We sought to identify the molecular mechanism, whereby variation at 1q24 may lead to AF susceptibility...
October 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28951744/igf1-and-nrg1-enhance-proliferation-metabolic-maturity-and-the-force-frequency-response-in-hesc-derived-engineered-cardiac-tissues
#8
Cassady E Rupert, Kareen L K Coulombe
Insulin-like growth factor 1 (IGF1) and neuregulin-1β (NRG1) play important roles during cardiac development both individually and synergistically. In this study, we analyze how 3D cardiac tissue engineered from human embryonic stem cell- (hESC-) derived cardiomyocytes and 2D-plated hESC-cardiomyocytes respond to developmentally relevant growth factors both to stimulate maturity and to characterize the therapeutic potential of IGF1 and NRG1. When administered to engineered cardiac tissues, a significant decrease in active force production of ~65% was measured in all treatment groups, likely due to changes in cellular physiology...
2017: Stem Cells International
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
#9
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
#10
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
#11
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
#12
Maj Linea Vestergaard, Søren Grubb, Karen Koefoed, Zoe Anderson-Jenkins, Kristina Grunnet-Lauridsen, Kirstine Calloe, Christian Clausen, Søren Tvorup Christensen, Kjeld Møllgård, Claus Yding Andersen
The derivation of functional cardiomyocytes (CMs) from human embryonic stem cells (hESCs) represents a unique way of studying human cardiogenesis, including the development of CM subtypes. In this study, we investigated the development and organization of hESC-derived cardiomyocytes (hESC-CMs) and examined how the expression levels 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...
November 1, 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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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