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Human embryonic stem cells derived cardiomyocytes

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https://www.readbyqxmd.com/read/29774076/the-human-somatostatin-receptor-type-2-as-an-imaging-and-suicide-reporter-gene-for-pluripotent-stem-cell-derived-therapy-of-myocardial-infarction
#1
Katrien Neyrinck, Natacha Breuls, Bryan Holvoet, Wouter Oosterlinck, Esther Wolfs, Hubert Vanbilloen, Olivier Gheysens, Robin Duelen, Willy Gsell, Ivo Lambrichts, Uwe Himmelreich, Catherine M Verfaillie, Maurilio Sampaolesi, Christophe M Deroose
Rationale: Pluripotent stem cells (PSCs) are being investigated as a cell source for regenerative medicine since they provide an infinitive pool of cells that are able to differentiate towards every cell type of the body. One possible therapeutic application involves the use of these cells to treat myocardial infarction (MI), a condition where billions of cardiomyocytes (CMs) are lost. Although several protocols have been developed to differentiate PSCs towards CMs, none of these provide a completely pure population, thereby still posing a risk for neoplastic teratoma formation...
2018: Theranostics
https://www.readbyqxmd.com/read/29758359/probing-flecainide-block-of-i-na-using-human-pluripotent-stem-cell-derived-ventricular-cardiomyocytes-adapted-to-automated-patch-clamping-and-2d-monolayers
#2
Lin Geng, Chi-Wing Kong, Andy O T Won, Angie Man-Yee Shum, Maggie Z Y Chow, Hui Che, Chenzi Zhang, Ka-Long Yau, Camie W Chan, Wendy Keung, Ronald A Li
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are emerging tools for applications such as drug discovery and screening for pro-arrhythmogenicity and cardiotoxicity as leading causes for drug attrition. Understanding the electrophysiology (EP) of hPSC-CMs is essential but conventional manual patch-clamping is highly laborious and low-throughput. Here we adapted hPSC-CMs derived from two human embryonic stem cell (hESC) lines, HES2 and H7, for a 16-channel automated planar-recording approach for single-cell EP characterization...
May 11, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29758225/trpv6-protects-er-stress-induced-apoptosis-via-atf6%C3%AE-trpv6-jnk-pathway-in-human-embryonic-stem-cell-derived-cardiomyocytes
#3
Zhichao Li, Zhaoyue Meng, Jun Lu, Francis M Chen, Wing-Tak Wong, Gary Tse, Changbo Zheng, Wendy Keung, Kennis Tse, Ronald A Li, Liwen Jiang, Xiaoqiang Yao
Human pluripotent stem cell-derived cardiomyocytes have potential applications in disease modeling and drug screening. Therefore, it is important to understand the mechanisms and signaling pathways underlying the survival and death of these cells. Endoplasmic reticulum (ER) stress is triggered by various cellular stresses that disturb protein folding in the ER. Cells cope with ER stress by activating the unfolded protein response (UPR), a homeostatic signaling network that orchestrates the recovery of ER function...
May 11, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29755568/exosomes-secreted-by-normoxic-and-hypoxic-cardiosphere-derived-cells-have-anti-apoptotic-effect
#4
Helia Namazi, Iman Namazi, Parisa Ghiasi, Hassan Ansari, Sarah Rajabi, Ensiyeh Hajizadeh-Saffar, Nasser Aghdami, Elham Mohit
Cardiosphere-derived cells (CDCs) have emerged as one of the most promising stem cell types for cardiac protection and repair. Exosomes are required for the regenerative effects of human CDCs and mimic the cardioprotective benefits of CDCs such as anti-apoptotic effect in animal myocardial infarction (MI) models. Here we aimed to investigate the anti-apoptotic effect of the hypoxic and normoxic human CDCs-derived exosomes on induced apoptosis in human embryonic stem cell-derived cardiomyocytes (hESC-CMs). In this study, CDCs were cultured under normoxic (18% O2 ) and hypoxic (1% O2 ) conditions and CDC-exosomes were isolated from conditioned media by differential ultracentrifugation...
2018: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/29739872/chemical-compound-based-direct-reprogramming-for-future-clinical-applications
#5
REVIEW
Yukimasa Takeda, Yoshinori Harada, Toshikazu Yoshikawa, Ping Dai
Recent studies have revealed that a combination of chemical compounds enables direct reprogramming from one somatic cell type into another without the use of transgenes by regulating cellular signaling pathways and epigenetic modifications. The generation of induced pluripotent stem (iPS) cells generally requires virus vector-mediated expression of multiple transcription factors, which might disrupt genomic integrity and proper cell functions. The direct reprogramming is a promising alternative to rapidly prepare different cell types by bypassing the pluripotent state...
June 29, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29698509/microrna-425-and-microrna-155-cooperatively-regulate-atrial-natriuretic-peptide-expression-and-cgmp-production
#6
Sara Vandenwijngaert, Clara D Ledsky, Obiajulu Agha, Connie Wu, Dongjian Hu, Aranya Bagchi, Ibrahim J Domian, Emmanuel S Buys, Christopher Newton-Cheh, Donald B Bloch
AIMS: Atrial natriuretic peptide (ANP), secreted primarily by atrial cardiomyocytes, decreases blood pressure by raising cyclic 3',5'-guanosine monophosphate (cGMP) levels and inducing vasorelaxation, natriuresis, and diuresis. Raising the level of ANP has been shown to be an effective treatment for hypertension. To advance the future development of an anti-microRNA (miR) approach to increasing expression of ANP, we investigated the regulation of NPPA expression by two miRs: miR-425 and miR-155...
2018: PloS One
https://www.readbyqxmd.com/read/29693249/yes-associated-protein-mediates-human-embryonic-stem-cell-derived-cardiomyocyte-proliferation-involvement-of-epidermal-growth-factor-receptor-signaling
#7
Somi Park, Museog Choe, Hancheol Yeo, Hojae Han, Joongsun Kim, Woocheol Chang, Seungpil Yun, Hojin Lee, Minyoung Lee
Unlike mature cardiomyocytes, human pluripotent stem cell-derived cardiomyocytes exhibit higher proliferative capacity; however, the underlying mechanisms involved are yet to be elucidated. Here, we revealed that the Yes-associated protein (YAP) plays a critical role in regulating cell proliferation in association with epidermal growth factor receptor (EGFR) in human embryonic stem cell-derived cardiomyocytes (hESC-CMs). Our results show that low-density culture significantly promotes the proliferation of hESC-CMs via YAP...
April 25, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29649238/generation-of-multidrug-resistant-human-tissues-by-overexpression-of-the-abcg2-multidrug-transporter-in-embryonic-stem-cells
#8
Zsuzsa Erdei, Anita Schamberger, György Török, Kornélia Szebényi, György Várady, Tamás I Orbán, László Homolya, Balázs Sarkadi, Ágota Apáti
The ABCG2 multidrug transporter provides resistance against various endo- and xenobiotics, and protects the stem cells against toxins and stress conditions. We have shown earlier that a GFP-tagged version of ABCG2 is fully functional and may be used to follow the expression, localization and function of this transporter in living cells. In the present work we have overexpressed GFP-ABCG2, driven by a constitutive (CAG) promoter, in HUES9 human embryonic stem cells. Stem cell clones were generated to express the wild-type and a substrate-mutant (R482G) GFP-ABCG2 variant, by using the Sleeping Beauty transposon system...
2018: PloS One
https://www.readbyqxmd.com/read/29555651/an-inactivating-mutation-in-the-histone-deacetylase-sirt6-causes-human-perinatal-lethality
#9
Christina M Ferrer, Marielle Alders, Alex V Postma, Seonmi Park, Mark A Klein, Murat Cetinbas, Eva Pajkrt, Astrid Glas, Silvana van Koningsbruggen, Vincent M Christoffels, Marcel M A M Mannens, Lia Knegt, Jean-Pierre Etchegaray, Ruslan I Sadreyev, John M Denu, Gustavo Mostoslavsky, Merel C van Maarle, Raul Mostoslavsky
It has been well established that histone and DNA modifications are critical to maintaining the equilibrium between pluripotency and differentiation during early embryogenesis. Mutations in key regulators of DNA methylation have shown that the balance between gene regulation and function is critical during neural development in early years of life. However, there have been no identified cases linking epigenetic regulators to aberrant human development and fetal demise. Here, we demonstrate that a homozygous inactivating mutation in the histone deacetylase SIRT6 results in severe congenital anomalies and perinatal lethality in four affected fetuses...
March 1, 2018: Genes & Development
https://www.readbyqxmd.com/read/29504165/electroconductive-biohybrid-collagen-pristine-graphene-composite-biomaterials-with-enhanced-biological-activity
#10
Alan J Ryan, Cathal J Kearney, Nian Shen, Umar Khan, Adam G Kelly, Christopher Probst, Eva Brauchle, Sonia Biccai, Carolina D Garciarena, Victor Vega-Mayoral, Peter Loskill, Steve W Kerrigan, Daniel J Kelly, Katja Schenke-Layland, Jonathan N Coleman, Fergal J O'Brien
Electroconductive substrates are emerging as promising functional materials for biomedical applications. Here, the development of biohybrids of collagen and pristine graphene that effectively harness both the biofunctionality of the protein component and the increased stiffness and enhanced electrical conductivity (matching native cardiac tissue) obtainable with pristine graphene is reported. As well as improving substrate physical properties, the addition of pristine graphene also enhances human cardiac fibroblast growth while simultaneously inhibiting bacterial attachment (Staphylococcus aureus)...
April 2018: Advanced Materials
https://www.readbyqxmd.com/read/29503094/prospective-isolation-of-isl1-cardiac-progenitors-from-human-escs-for-myocardial-infarction-therapy
#11
Zaniar Ghazizadeh, Faranak Fattahi, Mehdi Mirzaei, Delger Bayersaikhan, Jaesuk Lee, Sehyun Chae, Daehee Hwang, Kyunghee Byun, Mehdi Sharifi Tabar, Sara Taleahmad, Shahab Mirshahvaladi, Parisa Shabani, Hananeh Fonoudi, Paul A Haynes, Hossein Baharvand, Nasser Aghdami, Todd Evans, Bonghee Lee, Ghasem Hosseini Salekdeh
The LIM-homeodomain transcription factor ISL1 marks multipotent cardiac progenitors that give rise to cardiac muscle, endothelium, and smooth muscle cells. ISL1+ progenitors can be derived from human pluripotent stem cells, but the inability to efficiently isolate pure populations has limited their characterization. Using a genetic selection strategy, we were able to highly enrich ISL1+ cells derived from human embryonic stem cells. Comparative quantitative proteomic analysis of enriched ISL1+ cells identified ALCAM (CD166) as a surface marker that enabled the isolation of ISL1+ progenitor cells...
March 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29484788/iron-deficiency-impairs-contractility-of-human-cardiomyocytes-through-decreased-mitochondrial-function
#12
Martijn F Hoes, Niels Grote Beverborg, J David Kijlstra, Jeroen Kuipers, Dorine W Swinkels, Ben N G Giepmans, Richard J Rodenburg, Dirk J van Veldhuisen, Rudolf A de Boer, Peter van der Meer
AIMS: Iron deficiency is common in patients with heart failure and associated with a poor cardiac function and higher mortality. How iron deficiency impairs cardiac function on a cellular level in the human setting is unknown. This study aims to determine the direct effects of iron deficiency and iron repletion on human cardiomyocytes. METHODS AND RESULTS: Human embryonic stem cell-derived cardiomyocytes were depleted of iron by incubation with the iron chelator deferoxamine (DFO)...
May 2018: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29477480/dehydroevodiamine-and-hortiamine-alkaloids-from-the-traditional-chinese-herbal-drug-evodia-rutaecarpa-are-i-kr-blockers-with-proarrhythmic-effects-in-vitro-and-in-vivo
#13
Igor Baburin, Rosanne Varkevisser, Anja Schramm, Priyanka Saxena, Stanislav Beyl, Phillip Szkokan, Tobias Linder, Anna Stary-Weinzinger, Marcel A G van der Heyden, Marien Houtman, Hiroki Takanari, Malin Jonsson, Jet H D Beekman, Matthias Hamburger, Marc A Vos, Steffen Hering
Evodiae fructus is a widely used herbal drug in traditional Chinese medicine. Evodia extract was found to inhibit hERG channels. The aim of the current study was to identify hERG inhibitors in Evodia extract and to investigate their potential proarrhythmic effects. Dehydroevodiamine (DHE) and hortiamine were identified as IKr (rapid delayed rectifier current) inhibitors in Evodia extract by HPLC-microfractionation and subsequent patch clamp studies on human embryonic kidney cells. DHE and hortiamine inhibited IKr with IC50 s of 253...
May 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29456183/modeling-human-cardiac-hypertrophy-in-stem-cell-derived-cardiomyocytes
#14
Ekaterina Ovchinnikova, Martijn Hoes, Kirill Ustyantsev, Nils Bomer, Tristan V de Jong, Henny van der Mei, Eugene Berezikov, Peter van der Meer
Cardiac hypertrophy accompanies many forms of cardiovascular diseases. The mechanisms behind the development and regulation of cardiac hypertrophy in the human setting are poorly understood, which can be partially attributed to the lack of a human cardiomyocyte-based preclinical test system recapitulating features of diseased myocardium. The objective of our study is to determine whether human embryonic stem cell-derived cardiomyocytes (hESC-CMs) subjected to mechanical stretch can be used as an adequate in vitro model for studying molecular mechanisms of cardiac hypertrophy...
March 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29420830/acellular-therapeutic-approach-for-heart-failure-in-vitro-production-of-extracellular-vesicles-from-human-cardiovascular-progenitors
#15
Nadia El Harane, Anaïs Kervadec, Valérie Bellamy, Laetitia Pidial, Hany J Neametalla, Marie-Cécile Perier, Bruna Lima Correa, Léa Thiébault, Nicolas Cagnard, Angéline Duché, Camille Brunaud, Mathilde Lemitre, Jeanne Gauthier, Alexandra T Bourdillon, Marc P Renault, Yeranuhi Hovhannisyan, Solenne Paiva, Alexandre R Colas, Onnik Agbulut, Albert Hagège, Jean-Sébastien Silvestre, Philippe Menasché, Nisa K E Renault
Aims: We have shown that extracellular vesicles (EVs) secreted by embryonic stem cell-derived cardiovascular progenitor cells (Pg) recapitulate the therapeutic effects of their parent cells in a mouse model of chronic heart failure (CHF). Our objectives are to investigate whether EV released by more readily available cell sources are therapeutic, whether their effectiveness is influenced by the differentiation state of the secreting cell, and through which mechanisms they act. Methods and results: The total EV secreted by human induced pluripotent stem cell-derived cardiovascular progenitors (iPSC-Pg) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) were isolated by ultracentrifugation and characterized by Nanoparticle Tracking Analysis, western blot, and cryo-electron microscopy...
February 6, 2018: European Heart Journal
https://www.readbyqxmd.com/read/29373717/integrated-transcriptomic-and-regulatory-network-analyses-identify-microrna-200c-as-a-novel-repressor-of-human-pluripotent-stem-cell-derived-cardiomyocyte-differentiation-and-maturation
#16
Ellen Ngar Yun Poon, Baixia Hao, Daogang Guan, Mulin Jun Li, Jun Lu, Yong Yang, Binbin Wu, Stanley Chun Ming Wu, Sarah E Webb, Yan Liang, Andrew L Miller, Xiaoqiang Yao, Junwen Wang, Bin Yan, Kenneth R Boheler
Aims: MicroRNAs (miRNAs) are crucial for the post-transcriptional control of protein-encoding genes, and together with transcription factors (TFs) regulate gene expression; however, the regulatory activities of miRNAs during cardiac development are only partially understood. In this study, we tested the hypothesis that integrative computational approaches could identify miRNAs that experimentally could be shown to regulate cardiomyogenesis. Methods and results: We integrated expression profiles with bioinformatics analyses of miRNA and TF regulatory programs to identify candidate miRNAs involved with cardiac development...
January 24, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29348408/nipbl-haploinsufficiency-reveals-a-constellation-of-transcriptome-disruptions-in-the-pluripotent-and-cardiac-states
#17
Jason A Mills, Pamela S Herrera, Maninder Kaur, Lanfranco Leo, Deborah McEldrew, Jesus A Tintos-Hernandez, Ramakrishnan Rajagopalan, Alyssa Gagne, Zhe Zhang, Xilma R Ortiz-Gonzalez, Ian D Krantz
Cornelia de Lange syndrome (CdLS) is a complex disorder with multiple structural and developmental defects caused by mutations in structural and regulatory proteins involved in the cohesin complex. NIPBL, a cohesin regulatory protein, has been identified as a critical protein responsible for the orchestration of transcriptomic regulatory networks necessary for embryonic development. Mutations in NIPBL are responsible for the majority of cases of CdLS. Through RNA-sequencing of human induced pluripotent stem cells and in vitro-derived cardiomyocytes, we identified hundreds of mRNAs, pseudogenes, and non-coding RNAs with altered expression in NIPBL+/- patient-derived cells...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29336212/simulated-microgravity-impairs-cardiac-autonomic-neurogenesis-from-neural-crest-cells
#18
Konstantinos E Hatzistergos, Zhijie Jiang, Krystalenia Valasaki, Lauro M Takeuchi, Wayne Balkan, Preethi Atluri, Dieter Saur, Barbara Seidler, Nicholas Tsinoremas, Darcy L DiFede, Joshua M Hare
Microgravity-induced alterations in the autonomic nervous system (ANS) contribute to derangements in both the mechanical and electrophysiological function of the cardiovascular system, leading to severe symptoms in humans following space travel. Because the ANS forms embryonically from neural crest (NC) progenitors, we hypothesized that microgravity can impair NC-derived cardiac structures. Accordingly, we conducted in vitro simulated microgravity experiments employing NC genetic lineage tracing in mice with cKitCreERT2/+ , Isl1nLacZ, and Wnt1-Cre reporter alleles...
March 20, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29277329/human-embryonic-stem-cell-derived-cardiomyocytes-as-an-in-vitro-model-to-study-cardiac-insulin-resistance
#19
Ilvy M E Geraets, Dipanjan Chanda, Florence H J van Tienen, Arthur van den Wijngaard, Rick Kamps, Dietbert Neumann, Yilin Liu, Jan F C Glatz, Joost J F P Luiken, Miranda Nabben
Patients with type 2 diabetes (T2D) and/or insulin resistance (IR) have an increased risk for the development of heart failure (HF). Evidence indicates that this increased risk is linked to an altered cardiac substrate preference of the insulin resistant heart, which shifts from a balanced utilization of glucose and long-chain fatty acids (FAs) towards an almost complete reliance on FAs as main fuel source. This shift leads to a loss of endosomal proton pump activity and increased cardiac fat accumulation, which eventually triggers cardiac dysfunction...
December 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29243046/-stem-cell-based-cardiac-regeneration-after-myocardial-infarction
#20
REVIEW
M Reinsch, F Weinberger
Myocardial infarction leads to an irreversible loss of vital myocardial cells. The transplantation of new cardiomyocytes into the heart was first described over 20 years ago and represents a straightforward approach to remuscularize a damaged heart. Due to the lack of human cells a clinical application seemed ambitious; however, dramatic progress in stem cell biology over the last two decades has paved the way towards a clinical application. This is especially important as the prognosis for patients with terminal heart failure is still poor...
March 2018: Herz
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