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Human embryonic stem cells derived cardiomyocytes

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https://www.readbyqxmd.com/read/28219898/sk4-k-channels-are-therapeutic-targets-for-the-treatment-of-cardiac-arrhythmias
#1
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...
February 20, 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
#2
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-modelling-and-repair
#3
Malte Tiburcy, James E Hudson, Paul Balfanz, Susanne F Schlick, Tim Meyer, Mei-Ling Chang Liao, Elif Levent, Farah Raad, Sebastian Zeidler, Edgar Wingender, Johannes Riegler, Mouer Wang, Joseph D Gold, Itzhak Kehat, Erich Wettwer, Ursula Ravens, Pieterjan Dierickx, Linda van Laake, Marie-José 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 modelling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) towards 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...
February 6, 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
#4
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
#5
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
#6
Sarah Anna Konze, Sebastian Werneburg, Astrid Oberbeck, Ruth Olmer, Henning Kempf, Monica Jara-Avaca, Andreas Pich, Robert Zweigerdt, Falk Fritz Reinhold 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)...
January 31, 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
#7
Yin Wang, Shi-Qiang Wang, Li-Peng Wang, Yu-Hong Yao, Chun-Yan Ma, Jin-Feng Ding, Jue Ye, Xian-Min Meng, Rui-Xia Xu, Jian-Jun Li
: 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...
January 26, 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
#8
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...
February 15, 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
#9
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
#10
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
https://www.readbyqxmd.com/read/27890729/maturation-of-human-embryonic-stem-cell-derived-cardiomyocytes-hesc-cms-in-3d-collagen-matrix-effects-of-niche-cell-supplementation-and-mechanical-stimulation
#11
W Zhang, C W Kong, M H Tong, W H Chooi, N Huang, R A Li, B P Chan
: Cardiomyocytes derived from human embryonic stem cells (hESC-CMs) are regarded as a promising source for regenerative medicine, drug testing and disease modeling. Nevertheless, cardiomyocytes are immature in terms of their contractile structure, metabolism and electrophysiological properties. Here, we fabricate cardiac muscle strips by encapsulating hESC-CMs in collagen-based biomaterials. Supplementation of niche cells at 3% to the number of hESC-CMs enhance the maturation of the hESC-CMs in 3D tissue matrix...
November 24, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27866707/a-functional-variant-associated-with-atrial-fibrillation-regulates-pitx2c-expression-through-tfap2a
#12
Jiangchuan Ye, Nathan R Tucker, Lu-Chen Weng, Sebastian Clauss, Steven A Lubitz, Patrick T Ellinor
The most significantly associated genetic locus for atrial fibrillation (AF) is in chromosomal region 4q25, where four independent association signals have been identified. Although model-system studies suggest that altered PITX2c expression might underlie the association, the link between specific variants and the direction of effect on gene expression remains unknown for all four signals. In the present study, we analyzed the AF-associated region most proximal to PITX2 at 4q25. First, we identified candidate regulatory variants that might confer AF risk through a combination of mammalian conservation, DNase hypersensitivity, and histone modification from ENCODE and the Roadmap Epigenomics Project, as well as through in vivo analysis of enhancer activity in embryonic zebrafish...
December 1, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27861123/tecrl-a-new-life-threatening-inherited-arrhythmia-gene-associated-with-overlapping-clinical-features-of-both-lqts-and-cpvt
#13
Harsha D Devalla, Roselle Gélinas, Elhadi H Aburawi, Abdelaziz Beqqali, Philippe Goyette, Christian Freund, Marie-A Chaix, Rafik Tadros, Hui Jiang, Antony Le Béchec, Jantine J Monshouwer-Kloots, Tom Zwetsloot, Georgios Kosmidis, Frédéric Latour, Azadeh Alikashani, Maaike Hoekstra, Jurg Schlaepfer, Christine L Mummery, Brian Stevenson, Zoltan Kutalik, Antoine Af de Vries, Léna Rivard, Arthur Am Wilde, Mario Talajic, Arie O Verkerk, Lihadh Al-Gazali, John D Rioux, Zahurul A Bhuiyan, Robert Passier
Genetic causes of many familial arrhythmia syndromes remain elusive. In this study, whole-exome sequencing (WES) was carried out on patients from three different families that presented with life-threatening arrhythmias and high risk of sudden cardiac death (SCD). Two French Canadian probands carried identical homozygous rare variant in TECRL gene (p.Arg196Gln), which encodes the trans-2,3-enoyl-CoA reductase-like protein. Both patients had cardiac arrest, stress-induced atrial and ventricular tachycardia, and QT prolongation on adrenergic stimulation...
December 1, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27784737/readthrough-promoting-drugs-gentamicin-and-ptc124-fail-to-rescue-nav1-5-function-of-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-carrying-nonsense-mutations-in-the-sodium-channel-gene-scn5a
#14
Georgios Kosmidis, Christiaan C Veerman, Simona Casini, Arie O Verkerk, Simone van de Pas, Milena Bellin, Arthur A M Wilde, Christine L Mummery, Connie R Bezzina
BACKGROUND: Several compounds have been reported to induce translational readthrough of premature stop codons resulting in the production of full-length protein by interfering with ribosomal proofreading. Here we examined the effect of 2 of these compounds, gentamicin and PTC124, in human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes bearing nonsense mutations in the sodium channel gene SCN5A, which are associated with conduction disease and potential lethal arrhythmias...
November 2016: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/27743117/stiff-matrix-induces-switch-to-pure-%C3%AE-cardiac-myosin-heavy-chain-expression-in-human-esc-derived-cardiomyocytes
#15
Natalie Weber, Kristin Schwanke, Stephan Greten, Meike Wendland, Bogdan Iorga, Martin Fischer, Cornelia Geers-Knörr, Jan Hegermann, Christoph Wrede, Jan Fiedler, Henning Kempf, Annika Franke, Birgit Piep, Angelika Pfanne, Thomas Thum, Ulrich Martin, Bernhard Brenner, Robert Zweigerdt, Theresia Kraft
Human pluripotent stem cell (hPSC)-derived cardiomyocytes hold great potential for in vitro modeling of diseases like cardiomyopathies. Yet, knowledge about expression and functional impact of sarcomeric protein isoforms like the myosin heavy chain (MyHC) in hPSC-cardiomyocytes is scarce. We hypothesized that ventricular β-MyHC expression alters contraction and calcium kinetics and drives morphological and electrophysiological differentiation towards ventricular-like cardiomyocytes. To address this, we (1) generated human embryonic stem cell-derived cardiomyocytes (hESC-CMs) that switched towards exclusive β-MyHC, and (2) functionally and morphologically characterized these hESC-CMs at the single-cell level...
November 2016: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27722090/functional-high-resolution-time-course-expression-analysis-of-human-embryonic-stem-cells-undergoing-cardiac-induction
#16
Ilaria Piccini, Marcos Araúzo-Bravo, Guiscard Seebohm, Boris Greber
Cardiac induction of human embryonic stem cells (hESCs) is a process bearing increasing medical relevance, yet it is poorly understood from a developmental biology perspective. Anticipated technological progress in deriving stably expandable cardiac precursor cells or in advancing cardiac subtype specification protocols will likely require deeper insights into this fascinating system. Recent improvements in controlling hESC differentiation now enable a near-homogeneous induction of the cardiac lineage. This is based on an optimized initial stimulation of mesoderm-inducing signaling pathways such as Activin and/or FGF, BMP, and WNT, followed by WNT inhibition as a secondary requirement...
December 2016: Genomics Data
https://www.readbyqxmd.com/read/27677332/non-cell-autonomous-cues-for-enhanced-functionality-of-human-embryonic-stem-cell-derived-cardiomyocytes-via-maturation-of-sarcolemmal-and-mitochondrial-katp-channels
#17
Wendy Keung, Lihuan Ren, Sen Li, Andy On-Tik Wong, Anant Chopra, Chi-Wing Kong, Gordon F Tomaselli, Christopher S Chen, Ronald A Li
Human embryonic stem cells (hESCs) is a potential unlimited ex vivo source of ventricular (V) cardiomyocytes (CMs), but hESC-VCMs and their engineered tissues display immature traits. In adult VCMs, sarcolemmal (sarc) and mitochondrial (mito) ATP-sensitive potassium (KATP) channels play crucial roles in excitability and cardioprotection. In this study, we aim to investigate the biological roles and use of sarcKATP and mitoKATP in hESC-VCM. We showed that SarcIK, ATP in single hESC-VCMs was dormant under baseline conditions, but became markedly activated by cyanide (CN) or the known opener P1075 with a current density that was ~8-fold smaller than adult; These effects were reversible upon washout or the addition of GLI or HMR1098...
September 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27649385/embryonic-stem-like-cells-from-rabbit-blastocysts-cultured-with-melatonin-could-differentiate-into-three-germ-layers-in-vitro-and-in-vivo
#18
Ruxue Wei, Xueming Zhao, Haisheng Hao, Weihua Du, Huabin Zhu
The rabbit is considered an important model animal from which to obtain embryonic stem cells because of the utility of this animal in physiology and reproductive research. Here, we derived rabbit ES-like (rES-like) cells from blastocysts of superovulated Japanese white rabbits using culture medium containing 10(-7)  M melatonin, 10 ng/mL basic fibroblast growth factor, and 1,000 IU/mL human leukemia inhibitory factor. This concentration of melatonin had the most significant positive effects on the proliferation inner cell mass-derived cells (improving rates from 19...
November 2016: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/27643958/analysis-of-calcium-transients-and-uniaxial-contraction-force-in-single-human-embryonic-stem-cell-derived-cardiomyocytes-on-microstructured-elastic-substrate-with-spatially-controlled-surface-chemistries
#19
Eleonora Grespan, Sebastian Martewicz, Elena Serena, Vincent Le Houerou, Jürgen Rühe, Nicola Elvassore
The mechanical activity of cardiomyocytes is the result of a process called excitation-contraction coupling (ECC). A membrane depolarization wave induces a transient cytosolic calcium concentration increase that triggers activation of calcium-sensitive contractile proteins, leading to cell contraction and force generation. An experimental setup capable of acquiring simultaneously all ECC features would have an enormous impact on cardiac drug development and disease study. In this work, we develop a microengineered elastomeric substrate with tailor-made surface chemistry to measure simultaneously the uniaxial contraction force and the calcium transients generated by single human cardiomyocytes in vitro...
November 22, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/27637492/human-ips-cell-derived-cardiac-tissue-sheets-a-platform-for-cardiac-regeneration
#20
REVIEW
Hidetoshi Masumoto, Jun K Yamashita
Stem cell therapy is a promising therapeutic option for severe cardiac diseases that are resistant to conventional therapies. To overcome the unsatisfactory results of most clinical researches on stem cell injections to an injured heart, we are developing bioengineered cardiac tissue grafts using pluripotent stem cell-derived cardiomyocytes and vascular cells. We have validated the functional benefits of mouse embryonic stem cell-derived and human induced pluripotent stem cell-derived cardiac tissue sheets (CTSs) in a rat myocardial infarction model...
November 2016: Current Treatment Options in Cardiovascular Medicine
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