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Cardiomyocyte stem cells

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https://www.readbyqxmd.com/read/28329361/sex-hormones-affect-outcome-in-arrhythmogenic-right-ventricular-cardiomyopathy-dysplasia-from-a-stem-cell-derived-cardiomyocyte-based-model-to-clinical-biomarkers-of-disease-outcome
#1
Deniz Akdis, Ardan M Saguner, Khooshbu Shah, Chuanyu Wei, Argelia Medeiros-Domingo, Arnold von Eckardstein, Thomas F Lüscher, Corinna Brunckhorst, H S Vincent Chen, Firat Duru
Aims: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is characterized by fibrofatty infiltration of the myocardium and ventricular arrhythmias that may lead to sudden cardiac death. It has been observed that male patients develop the disease earlier and present with more severe phenotypes as compared to females. Thus, we hypothesized that serum levels of sex hormones may contribute to major arrhythmic cardiovascular events (MACE) in patients with ARVC/D. Methods and results: The serum levels of five sex hormones, sex hormone-binding globulin, high sensitivity troponin T, pro-brain natriuretic peptide, cholesterol, triglycerides, insulin, and glucose were measured in 54 ARVC/D patients (72% male)...
February 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28327633/cardiac-drug-drug-interaction-between-hcv-ns5b-pronucleotide-inhibitors-and-amiodarone-is-determined-by-their-specific-diastereochemistry
#2
Armando Lagrutta, Christopher P Regan, Haoyu Zeng, John P Imredy, Kenneth Koeplinger, Pierre Morissette, Liping Liu, Gordon Wollenberg, Christopher Brynczka, José Lebrón, Joseph DeGeorge, Frederick Sannajust
Severe bradycardia/bradyarrhythmia following coadministration of the HCV-NS5B prodrug sofosbuvir with amiodarone was recently reported. Our previous preclinical in vivo experiments demonstrated that only certain HCV-NS5B prodrugs elicit bradycardia when combined with amiodarone. In this study, we evaluate the impact of HCV-NS5B prodrug phosphoramidate diastereochemistry (D-/L-alanine, R-/S-phosphoryl) in vitro and in vivo. Co-applied with amiodarone, L-ala,SP prodrugs increased beating rate and decreased beat amplitude in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), but D-ala,RP produgs, including MK-3682, did not...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327614/partial-reprogramming-of-pluripotent-stem-cell-derived-cardiomyocytes-into-neurons
#3
Wenpo Chuang, Arun Sharma, Praveen Shukla, Guang Li, Moritz Mall, Kuppusamy Rajarajan, Oscar J Abilez, Ryoko Hamaguchi, Joseph C Wu, Marius Wernig, Sean M Wu
Direct reprogramming of somatic cells has been demonstrated, however, it is unknown whether electrophysiologically-active somatic cells derived from separate germ layers can be interconverted. We demonstrate that partial direct reprogramming of mesoderm-derived cardiomyocytes into neurons is feasible, generating cells exhibiting structural and electrophysiological properties of both cardiomyocytes and neurons. Human and mouse pluripotent stem cell-derived CMs (PSC-CMs) were transduced with the neurogenic transcription factors Brn2, Ascl1, Myt1l and NeuroD...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325684/monitoring-and-visualizing-microrna-dynamics-during-live-cell-differentiation-using-microrna-responsive-non-viral-reporter-vectors
#4
Hideyuki Nakanishi, Kenji Miki, Kaoru R Komatsu, Masayuki Umeda, Megumi Mochizuki, Azusa Inagaki, Yoshinori Yoshida, Hirohide Saito
MicroRNA (miRNA) activity differs with cell type, suggesting it can be used as a cell marker. In this study, we developed novel miRNA-responsive non-viral reporter vectors to continuously monitor and visualize miRNA dynamics during differentiation and to efficiently purify target living cells. Each vector codes miRNA-responsive and reference reporter genes in a single mRNA. These two genes are independent modules but transcribed by a single promoter, which enables us to distinguish miRNA-mediated post-transcriptional repression from transcriptional repression...
March 2, 2017: Biomaterials
https://www.readbyqxmd.com/read/28321048/evaluation-of-the-effects-of-power-frequency-magnetic-fields-on-the-electrical-activity-of-cardiomyocytes-differentiated-from-human-induced-pluripotent-stem-cells
#5
Masayuki Takahashi, Atsushi Saito, Yasuhiko Jimbo, Satoshi Nakasono
Although cardiac activity is known to differ between species in many respects, most evaluations of the cardiac effects of low-frequency electric and magnetic fields, which have a stimulant effect on electrically activated cells, have been performed in non-human experimental animals and cells, and the effects in humans have been assessed using theoretical models. In recent years, it has been verified that human cardiomyocytes differentiated from human induced pluripotent stem cells (hiPS-CM) are useful for evaluating human responses to various cardioactive compounds...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28321045/characterization-of-human-ips-cell-derived-cardiomyocyte-sheets-as-a-model-to-detect-drug-induced-conduction-disturbance
#6
Hiroko Izumi-Nakaseko, Yuji Nakamura, Takeshi Wada, Kentaro Ando, Yasunari Kanda, Yuko Sekino, Atsushi Sugiyama
In order to characterize human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) sheets as a model for detecting drug-induced conduction disturbance, we examined their electrophysiological and electropharmacological properties by using the multi-electrode array system with a programmed electrical stimulation protocol. At pre-drug control, the conduction speed, effective refractory period and field potential duration were 0.14 ± 0.01 m/sec, 453 ± 10 msec and 361 ± 9 msec, respectively at a cycle length of 1,000 msec (n = 18)...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28320859/2-arachidonoylglycerol-ameliorates-inflammatory-stress-induced-insulin-resistance-in-cardiomyocytes
#7
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 the endocannabinoid 2-Arachidonoylglycerol (2-AG) via stimulation of cannabinoid type-1 (CB1) receptor and Ca2+/Calmodulin-dependent protein kinase β (CaMKKβ) activates AMPK leading to increased glucose uptake...
March 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28315121/untangling-the-biology-of-genetic-cardiomyopathies-with-pluripotent-stem-cell-disease-models
#8
REVIEW
Jan W Buikema, Sean M Wu
PURPOSE OF REVIEW: Recently, the discovery of strategies to reprogram somatic cells into induced pluripotent stem (iPS) cells has led to a major paradigm change in developmental and stem cell biology. The application of iPS cells and their cardiac progeny has opened novel directions to study cardiomyopathies at a cellular and molecular level. This review discusses approaches currently undertaken to unravel known inherited cardiomyopathies in a dish. RECENT FINDINGS: With improved efficiency for mutation correction by genome editing, human iPS cells have now provided a platform to untangle the biology of cardiomyopathies...
April 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28300219/doxorubicin-induces-cardiotoxicity-through-upregulation-of-death-receptors-mediated-apoptosis-in-cardiomyocytes
#9
Liqun Zhao, Baolin Zhang
Doxorubicin is a highly effective anticancer agent but causes cardiotoxicity in many patients. The mechanisms of doxorubicin-induced cardiotoxicity remain incompletely understood. Here we investigated doxorubicin-induced cytotoxicity in human induced pluripotent stem cells-derived cardiomyocytes (iPS-CMs). We found that doxorubicin and related anthracycline agents (e.g., daunorubicin, idarubicin, and epirubicin) significantly upregulated the expression of death receptors (DRs) (TNFR1, Fas, DR4 and DR5) in iPS-derived cardiomyocytes at both protein and mRNA levels...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298296/fabrication-of-synthetic-mesenchymal-stem-cells-for-the-treatment-of-acute-myocardial-infarction-in-mice
#10
Lan Luo, Junnan Tang, Kodai Nishi, Chen Yan, Phuong-Uyen Dinh, Jhon Cores, Takashi Kudo, Jinying Zhang, Tao-Sheng Li, Ke Cheng
Rationale: Stem cell therapy faces a number of challenges. It is difficult to grow, preserve, and transport stem cells before they are administered to the patient. Synthetic analogs for stem cells represent a new approach to overcome these hurdles and hold the potential to revolutionize regenerative medicine. Objective: We aim to fabricate synthetic analogs of stem cells and test their therapeutic potential for treatment of acute myocardial infarction in mice. Methods and Results: We packaged secreted factors from human bone marrow-derived mesenchymal stem cells (MSC) into Poly(lactic-co-glycolic acid) PLGA microparticles and then coated them with MSC membranes...
March 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28295371/remuscularization-of-the-failing-heart
#11
Wolfram-Hubertus Zimmermann
Myocardial remuscularization can be achieved by cardiomyocyte implantation. Electromechanical integration and long-term survival of cardiomyocyte grafts are essential for maximal therapeutic impact. Cardiomyocyte application with support material has been instrumental to enhance cell retention. Co-administration of pro-survival factors and immunological matching are additional strategies for increased cell graft survival. Finally, larger cardiomyocyte grafts, although therapeutically desirable, will increase the risk for arrhythmias and, if pluripotent stem cells are used to derive cardiomyocytes, tumor formation...
March 10, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28295048/cardiac-repair-in-a-mouse-model-of-acute-myocardial-infarction-with-trophoblast-stem-cells
#12
Guannan Li, Jianzhou Chen, Xinlin Zhang, Guixin He, Wei Tan, Han Wu, Ran Li, Yuhan Chen, Rong Gu, Jun Xie, Biao Xu
Various stem cells have been explored for the purpose of cardiac repair. However, any individual stem cell population has not been considered as the ideal source. Recently, trophoblast stem cells (TSCs), a newly described stem cell type, have demonstrated extensive plasticity. The present study evaluated the therapeutic effect of TSCs transplantation for heart regeneration in a mouse model of myocardial infarction (MI) and made a direct comparison with the most commonly used mesenchymal stem cells (MSCs). Transplantation of TSCs and MSCs led to a remarkably improved cardiac function in contrast with the PBS control, but only the TSCs exhibited the potential of differentiation into cardiomyocytes in vivo...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28290476/emerin-plays-a-crucial-role-in-nuclear-invagination-and-in-the-nuclear-calcium-transient
#13
Masaya Shimojima, Shinsuke Yuasa, Chikaaki Motoda, Gakuto Yozu, Toshihiro Nagai, Shogo Ito, Mark Lachmann, Shin Kashimura, Makoto Takei, Dai Kusumoto, Akira Kunitomi, Nozomi Hayashiji, Tomohisa Seki, Shugo Tohyama, Hisayuki Hashimoto, Masaki Kodaira, Toru Egashira, Kenshi Hayashi, Chiaki Nakanishi, Kenji Sakata, Masakazu Yamagishi, Keiichi Fukuda
Alteration of the nuclear Ca(2+) transient is an early event in cardiac remodeling. Regulation of the nuclear Ca(2+) transient is partly independent of the cytosolic Ca(2+) transient in cardiomyocytes. One nuclear membrane protein, emerin, is encoded by EMD, and an EMD mutation causes Emery-Dreifuss muscular dystrophy (EDMD). It remains unclear whether emerin is involved in nuclear Ca(2+) homeostasis. The aim of this study is to elucidate the role of emerin in rat cardiomyocytes by means of hypertrophic stimuli and in EDMD induced pluripotent stem (iPS) cell-derived cardiomyocytes in terms of nuclear structure and the Ca(2+) transient...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28288859/mitochondrial-toxicity-of-perfluorooctane-sulfonate-in-mouse-embryonic-stem-cell-derived-cardiomyocytes
#14
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...
March 10, 2017: Toxicology
https://www.readbyqxmd.com/read/28288171/the-acceleration-of-cardiomyogenesis-in-embryonic-stem-cells-in-vitro-by-serum-depletion-does-not-increase-the-number-of-developed-cardiomyocytes
#15
Katarzyna Anna Radaszkiewicz, Dominika Sýkorová, Lucia Binó, Jana Kudová, Markéta Bébarová, Jiřina Procházková, Hana Kotasová, Lukáš Kubala, Jiří Pacherník
The differentiation of pluripotent embryonic stem (ES) cells into various lineages in vitro represents an important tool for studying the mechanisms underlying mammalian embryogenesis. It is a key technique in studies evaluating the molecular mechanisms of cardiomyogenesis and heart development and also in embryotoxicology. Herein, modest modifications of the basic protocol for ES cell differentiation into cardiomyocytes were evaluated in order to increase the yield and differentiation status of developed cardiomyocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28287249/mtorc1-and-mtorc2-play-different-roles-in-regulating-cardiomyocyte-differentiation-from-embryonic-stem-cells
#16
Bei Zheng, Jiadan Wang, Leilei Tang, Jiana Shi, Danyan Zhu
Mammalian target of rapamycin (mTOR) is a serine/threonine kinase and functions through two distinct complexes, mTOR complex 1 (mTORC1) and complex 2 (mTORC2), with their key components Raptor and Rictor, to play crucial roles in cellular survival and growth. However, the roles of mTORC1 and mTORC2 in regulating cardiomyocyte differentiation from mouse embryonic stem (mES) cells are not clear. In this study, we performed Raptor or Rictor knockdown experiments to investigate the roles of mTORC1 and mTORC2 in cardiomyocyte differentiation...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28286266/diabetes-induced-effects-on-cardiomyocytes-in-chick-embryonic-heart-micromass-and-mouse-embryonic-d3-differentiated-stem-cells
#17
Omar J Mohammed, Muhammad Liaque Latif, Margaret K Pratten
Diabetes mellitus during pregnancy is a considerable medical challenge, since it is related to ‎augmented morbidity and mortality concerns for both the fetus ‎and the pregnant woman. Records show that the etiology of diabetic ‎embryopathy is complicated, as many teratological factors might be involved ‎in the mechanisms of diabetes mellitus-induced congenital malformation. ‎In this study, the potential cardiotoxic effect of hyperglycemia with hyperketonemia was investigated by using two in vitro models; primary chick embryonic cardiomyocytes and stem cell derived cardiomyocytes, where adverse effects were recorded in both systems...
March 9, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28279973/three-dimensional-cardiac-microtissues-composed-of-cardiomyocytes-and-endothelial-cells-co-differentiated-from-human-pluripotent-stem-cells
#18
Elisa Giacomelli, Milena Bellin, Luca Sala, Berend J van Meer, Leon G J Tertoolen, Valeria V Orlova, Christine L Mummery
Cardiomyocytes and endothelial cells in the heart are in close proximity and in constant dialogue. Endothelium regulates the size of the heart, supplies oxygen to the myocardium and secretes factors that support cardiomyocyte function. Robust and predictive cardiac disease models that faithfully recapitulate native human physiology in vitro would therefore ideally incorporate this cardiomyocyte-endothelium crosstalk. Here, we have generated and characterized human cardiac microtissues in vitro that integrate both cell types in complex 3D structures...
March 15, 2017: Development
https://www.readbyqxmd.com/read/28279214/cardiotoxicity-evaluation-using-human-embryonic-stem-cells-and-induced-pluripotent-stem-cell-derived-cardiomyocytes
#19
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/28266620/two-dimensional-electrophysiological-characterization-of-human-pluripotent-stem-cell-derived-cardiomyocyte-system
#20
Huanqi Zhu, Kelsey S Scharnhorst, Adam Z Stieg, James K Gimzewski, Itsunari Minami, Norio Nakatsuji, Haruko Nakano, Atsushi Nakano
Stem cell-derived cardiomyocytes provide a promising tool for human developmental biology, regenerative therapies, disease modeling, and drug discovery. As human pluripotent stem cell-derived cardiomyocytes remain functionally fetal-type, close monitoring of electrophysiological maturation is critical for their further application to biology and translation. However, to date, electrophysiological analyses of stem cell-derived cardiomyocytes has largely been limited by biologically undefined factors including 3D nature of embryoid body, sera from animals, and the feeder cells isolated from mouse...
March 7, 2017: Scientific Reports
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