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Human embryonic stem cells derived cardiomyocytes

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https://www.readbyqxmd.com/read/28550304/electronic-supplementary-materialidentification-of-a-na-k-atpase-inhibition-independent-proarrhythmic-ionic-mechanisms-of-cardiac-glycosides
#1
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
#2
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
#3
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...
May 23, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28528699/steps-toward-maturation-of-embryonic-stem-cell-derived-cardiomyocytes-by-defined-physical-signals
#4
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...
May 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28524367/transplantation-of-human-villous-trophoblasts-preserves-cardiac-function-in-mice-with-acute-myocardial-infarction
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28219898/sk4-k-channels-are-therapeutic-targets-for-the-treatment-of-cardiac-arrhythmias
#11
Shiraz Haron-Khun, David Weisbrod, Hanna Bueno, Dor Yadin, Joachim Behar, Asher Peretz, Ofer Binah, Edith Hochhauser, Michael Eldar, Yael Yaniv, Michael Arad, Bernard Attali
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a stress-provoked ventricular arrhythmia, which also manifests sinoatrial node (SAN) dysfunction. We recently showed that SK4 calcium-activated potassium channels are important for automaticity of cardiomyocytes derived from human embryonic stem cells. Here SK4 channels were identified in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from healthy and CPVT2 patients bearing a mutation in calsequestrin 2 (CASQ2-D307H) and in SAN cells from WT and CASQ2-D307H knock-in (KI) mice...
April 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28169114/coculturing-with-endothelial-cells-promotes-in-vitro-maturation-and-electrical-coupling-of-human-embryonic-stem-cell-derived-cardiomyocytes
#12
Jennifer Pasquier, Renuka Gupta, Damien Rioult, Jessica Hoarau-Véchot, Raphael Courjaret, Khaled Machaca, Jassim Al Suwaidi, Edouard G Stanley, Shahin Rafii, David A Elliott, Charbel Abi Khalil, Arash Rafii
BACKGROUND: Pluripotent human embryonic stem cells (hESC) are a promising source of repopulating cardiomyocytes. We hypothesized that we could improve maturation of cardiomyocytes and facilitate electrical interconnections by creating a model that more closely resembles heart tissue; that is, containing both endothelial cells (ECs) and cardiomyocytes. METHODS: We induced cardiomyocyte differentiation in the coculture of an hESC line expressing the cardiac reporter NKX2...
January 10, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28167635/defined-engineered-human-myocardium-with-advanced-maturation-for-applications-in-heart-failure-modeling-and-repair
#13
Malte Tiburcy, James E Hudson, Paul Balfanz, Susanne Schlick, Tim Meyer, Mei-Ling Chang Liao, Elif Levent, Farah Raad, Sebastian Zeidler, Edgar Wingender, Johannes Riegler, Mouer Wang, Joseph D Gold, Izhak Kehat, Erich Wettwer, Ursula Ravens, Pieterjan Dierickx, Linda W van Laake, Marie Jose Goumans, Sara Khadjeh, Karl Toischer, Gerd Hasenfuss, Larry A Couture, Andreas Unger, Wolfgang A Linke, Toshiyuki Araki, Benjamin Neel, Gordon Keller, Lior Gepstein, Joseph C Wu, Wolfram-Hubertus Zimmermann
BACKGROUND: Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modeling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) toward an adult phenotype under defined conditions. METHODS: We systematically investigated cell composition, matrix, and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions...
May 9, 2017: Circulation
https://www.readbyqxmd.com/read/28163723/activin-a-modulates-cripto-1-hnf4%C3%AE-cells-to-guide-cardiac-differentiation-from-human-embryonic-stem-cells
#14
Robin Duelen, Guillaume Gilbert, Abdulsamie Patel, Nathalie de Schaetzen, Liesbeth De Waele, Llewelyn Roderick, Karin R Sipido, Catherine M Verfaillie, Gunnar M Buyse, Lieven Thorrez, Maurilio Sampaolesi
The use of human pluripotent stem cells in basic and translational cardiac research requires efficient differentiation protocols towards cardiomyocytes. In vitro differentiation yields heterogeneous populations of ventricular-, atrial-, and nodal-like cells hindering their potential applications in regenerative therapies. We described the effect of the growth factor Activin A during early human embryonic stem cell fate determination in cardiac differentiation. Addition of high levels of Activin A during embryoid body cardiac differentiation augmented the generation of endoderm derivatives, which in turn promoted cardiomyocyte differentiation...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28153730/interpretation-of-field-potentials-measured-on-a-multi-electrode-array-in-pharmacological-toxicity-screening-on-primary-and-human-pluripotent-stem-cell-derived-cardiomyocytes
#15
L G J Tertoolen, S R Braam, B J van Meer, R Passier, C L Mummery
Multi electrode arrays (MEAs) are increasingly used to detect external field potentials in electrically active cells. Recently, in combination with cardiomyocytes derived from human (induced) pluripotent stem cells they have started to become a preferred tool to examine newly developed drugs for potential cardiac toxicity in pre-clinical safety pharmacology. The most important risk parameter is proarrhythmic activity in cardiomyocytes which can cause sudden cardiac death. Whilst MEAs can provide medium- to high- throughput noninvasive assay platform, the translation of a field potential to cardiac action potential (normally measured by low-throughput patch clamp) is complex so that accurate assessment of drug risk to the heart is in practice still challenging...
January 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28139119/proteomic-analysis-of-human-pluripotent-stem-cell-cardiomyogenesis-revealed-altered-expression-of-metabolic-enzymes-and-pdlim5-isoforms
#16
Sarah A Konze, Sebastian Werneburg, Astrid Oberbeck, Ruth Olmer, Henning Kempf, Monica Jara-Avaca, Andreas Pich, Robert Zweigerdt, Falk F R Buettner
Human pluripotent stem cells (hPSCs), both embryonic (hESCs) and induced (hiPSCs), can be differentiated into derivatives of the three germ layers and are promising tools in regenerative medicine. Cardiovascular diseases are the top-ranking cause of premature death worldwide, and cell replacement therapies based on in vitro differentiated cardiomyocytes might provide a promising perspective to cure patients in the future. The molecular processes during hPSC cardiomyogenesis are far from being fully understood, and we thus have focused here on characterizing the proteome along hESC in vitro differentiation into cardiomyocytes (CMs)...
February 14, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28135716/overexpression-of-cardiac-specific-kinase-tnni3k-promotes-mouse-embryonic-stem-cells-differentiation-into-cardiomyocytes
#17
Yin Wang, Shi-Qiang Wang, Li-Peng Wang, Yu-Hong Yao, Chun-Yan Ma, Jin-Feng Ding, Jue Ye, Xian-Min Meng, Jian-Jun Li, Rui-Xia Xu
Backgroud/Aims: The biological function of cardiac troponin I-interacting kinase (TNNI3K), a cardiac-specific functional kinase, is largely unknown. We investigated the effect of human TNNI3K (hTNNI3K) on the differentiation of mouse embryonic stem cells (mESCs) into cardiomyocytes. METHODS: First, the time-space expression of endogenous Tnni3k was detected by real-time polymerase chain reaction (PCR) and western blotting at 16 different time-points over a period of 28 days. Further, action potentials and calcium current with/without 5 µM nifedipine were measured by patch clamp for mESC-derived cardiomyocytes...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28116894/enhanced-cardiac-differentiation-of-human-cardiovascular-disease-patient-specific-induced-pluripotent-stem-cells-by-applying-unidirectional-electrical-pulses-using-aligned-electroactive-nanofibrous-scaffolds
#18
Leila Mohammadi Amirabad, Mohammad Massumi, Mehdi Shamsara, Iman Shabani, Afshin Amari, Majid Mossahebi Mohammadi, Simzar Hosseinzadeh, Saeid Vakilian, Sarah K Steinbach, Mohammad R Khorramizadeh, Masoud Soleimani, Jalal Barzin
In the embryonic heart, electrical impulses propagate in a unidirectional manner from the sinus venosus and appear to be involved in cardiogenesis. In this work, aligned and random polyaniline/polyetersulfone (PANI/PES) nanofibrous scaffolds doped by Camphor-10-sulfonic acid (β) (CPSA) were fabricated via electrospinning and used to conduct electrical impulses in a unidirectional and multidirectional fashion, respectively. A bioreactor was subsequently engineered to apply electrical impulses to cells cultured on PANI/PES scaffolds...
March 1, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27943600/generation-of-clinical-grade-functional-cardiomyocytes-from-human-embryonic-stem-cells-in-chemically-defined-conditions
#19
Yuanqing Tan, Pengcheng Han, Qi Gu, Gang Chen, Lei Wang, Ruoyu Ma, Jun Wu, Chunjing Feng, Ying Zhang, Liu Wang, Baoyang Hu, Wei Li, Jie Hao, Qi Zhou
A highly efficient cardiac differentiation from human pluripotent stem cells (hPSCs) is achievable using existing methods, especially with the standard B27 induction system. However, bovine serum albumin (BSA), one of the essential ingredients in B27, may pose significant complications for clinical studies owing to its animal origin and potential risks of virus contamination. Furthermore, the high cost of B27 induction system also limits the applications of hPSCs-derived cardiomyocytes. Here, we have developed a BSA-free and chemically defined medium (named VN) for differentiating hPSCs to clinical-grade cardiomyocytes which generated over 80% cTNT-positive cardiomyocytes with high yield...
December 12, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27903535/magnetic-resonance-imaging-of-cardiac-strain-pattern-following-transplantation-of-human-tissue-engineered-heart-muscles
#20
Xulei Qin, Johannes Riegler, Malte Tiburcy, Xin Zhao, Tony Chour, Babacar Ndoye, Michael Nguyen, Jackson Adams, Mohamed Ameen, Thomas S Denney, Phillip C Yang, Patricia Nguyen, Wolfram H Zimmermann, Joseph C Wu
BACKGROUND: The use of tissue engineering approaches in combination with exogenously produced cardiomyocytes offers the potential to restore contractile function after myocardial injury. However, current techniques assessing changes in global cardiac performance after such treatments are plagued by relatively low detection ability. Since the treatment is locally performed, this detection could be improved by myocardial strain imaging that measures regional contractility. METHODS AND RESULTS: Tissue engineered heart muscles (EHMs) were generated by casting human embryonic stem cell-derived cardiomyocytes with collagen in preformed molds...
November 2016: Circulation. Cardiovascular Imaging
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