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Human embryonic stem cells derived cardiomyocytes

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)...
March 5, 2018: Advanced Materials
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...
February 23, 2018: Stem Cell Reports
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)...
February 27, 2018: European Journal of Heart Failure
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...
February 22, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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...
February 8, 2018: Stem Cell Reports
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
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
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
Konstantinos E Hatzistergos, Zhijie Jiang, Krystalenia Valasaki, Lauro M Takeuchi, Wayne Balkan, Preethi Atluri, Dieter Saur, Barbara Seidler, Nicholas Tsinoremas, Darcy DiFede, Joshua M Hare
Microgravity-induced alterations in the autonomic nervous system (ANS) contribute to derangements in both the mechanical and electrophysiologic function of the cardiovascular system, leading to severe symptoms in humans following space travel. Because the ANS forms embryonically from neural crest progenitors (NCs), 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...
January 16, 2018: Stem Cells and Development
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
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...
December 14, 2017: Herz
Nermeen Eldabah, Erastus Nembu Nembo, Marina Penner, Judith Semmler, Rania Swelem, Amina Hassab, Marek Molcanyi, Jürgen Hescheler, Filomain Nguemo
Pluripotent stem cells have demonstrated the potential to generate large numbers of functional cardiomyocytes (CMs) from different cell sources. Besides Wnt signaling, additional pathways are involved in early cardiac development and function. To date however, no study exists showing the effects of perturbing the canonical Wnt pathway using nonhuman primate embryonic stem (ES) cells. In this study, we investigated the effect of canonical Wnt inhibition during differentiation of nonhuman primate ES cell-derived CMs under defined, growth factor conditions...
March 1, 2018: Stem Cells and Development
Xiaobing Tan, Qingli Dai, Tao Guo, Jingshu Xu, Qingyuan Dai
Advance in stem cell research resulted in several processes to generate induced pluripotent stem cells (iPSCs) from adult somatic cells. In our previous study, the reprogramming of iPSCs from human dental mesenchymal stem cells (MSCs) including SCAP and DPSCs, has been reported. Herein, safe iPSCs were reprogrammed from SCAP and DPSCs using non-integrating RNA virus vector, which is an RNA virus carrying no risk of altering host genome. DPSCs- and SCAP-derived iPSCs exhibited the characteristics of the classical morphology with human embryonic stem cells (hESCs) without integration of foreign genes, indicating the potential of their clinical application...
January 22, 2018: Biochemical and Biophysical Research Communications
Ming-Tao Zhao, Haodong Chen, Qing Liu, Ning-Yi Shao, Nazish Sayed, Hung-Ta Wo, Joe Z Zhang, Sang-Ging Ong, Chun Liu, Youngkyun Kim, Huaxiao Yang, Tony Chour, Hong Ma, Nuria Marti Gutierrez, Ioannis Karakikes, Shoukhrat Mitalipov, Michael P Snyder, Joseph C Wu
Patient-specific pluripotent stem cells (PSCs) can be generated via nuclear reprogramming by transcription factors (i.e., induced pluripotent stem cells, iPSCs) or by somatic cell nuclear transfer (SCNT). However, abnormalities and preclinical application of differentiated cells generated by different reprogramming mechanisms have yet to be evaluated. Here we investigated the molecular and functional features, and drug response of cardiomyocytes (PSC-CMs) and endothelial cells (PSC-ECs) derived from genetically relevant sets of human iPSCs, SCNT-derived embryonic stem cells (nt-ESCs), as well as in vitro fertilization embryo-derived ESCs (IVF-ESCs)...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
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...
March 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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
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
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
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
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
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