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Cardiomyocyte stem cells

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https://www.readbyqxmd.com/read/28440472/human-umbilical-cord-mesenchymal-stem-cells-alleviate-acute-myocarditis-by-modulating-endoplasmic-reticulum-stress-and-extracellular-signal-regulated-1-2-mediated-apoptosis
#1
Changyi Zhang, Guichi Zhou, Chanxin Cai, Jindi Li, Fen Chen, Lichun Xie, Wei Wang, Yonggang Zhang, Xiulan Lai, Lian Ma
Acute myocarditis is a non-ischemic inflammatory disease of the myocardium, and there is currently no standard treatment. Mesenchymal stem cells (MSCs) can alleviate myosin‑induced myocarditis; however, the mechanism has not been clearly elucidated. In the present study, the authors investigated the ability of human umbilical cordMSCs (HuMSCs) to attenuate myocardial injury and dysfunction during the acute phase of experimental myocarditis. Male Lewis rats (aged 8 weeks) were injected with porcine myosin to induce myocarditis...
April 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28439945/enhancement-of-cardiomyogenesis-in-murine-stem-cells-by-low-intensity-ultrasound
#2
Ailing Teo, Amir Morshedi, Jen-Chieh Wang, Yufeng Zhou, Mayasari Lim
OBJECTIVES: Low-intensity ultrasound (LIUS) has been shown to enhance bone and cartilage regeneration from stem cells. The ease of its incorporation makes it an attractive mechanical stimulus for not only osteogenesis and chondrogenesis, but also cardiomyogenesis. However, to date, no study has investigated its effects on cardiomyogenesis from embryonic stem cells. METHODS: In this study, murine embryonic stem cells were differentiated via embryoid body formation and plating, and after 3 days they were subjected to daily 10 minutes of LIUS treatment with various conditions: (1) low-pulsed (21 mW/cm(2) , 20% duty cycle), (2) low-continuous, (3) high-pulsed (147 mW/cm(2) , 20% duty cycle), and (4) high-continuous LIUS...
April 25, 2017: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
https://www.readbyqxmd.com/read/28439558/crispr-cpf1-correction-of-muscular-dystrophy-mutations-in-human-cardiomyocytes-and-mice
#3
Yu Zhang, Chengzu Long, Hui Li, John R McAnally, Kedryn K Baskin, John M Shelton, Rhonda Bassel-Duby, Eric N Olson
Duchenne muscular dystrophy (DMD), caused by mutations in the X-linked dystrophin gene (DMD), is characterized by fatal degeneration of striated muscles. Dilated cardiomyopathy is one of the most common lethal features of the disease. We deployed Cpf1, a unique class 2 CRISPR (clustered regularly interspaced short palindromic repeats) effector, to correct DMD mutations in patient-derived induced pluripotent stem cells (iPSCs) and mdx mice, an animal model of DMD. Cpf1-mediated genomic editing of human iPSCs, either by skipping of an out-of-frame DMD exon or by correcting a nonsense mutation, restored dystrophin expression after differentiation to cardiomyocytes and enhanced contractile function...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28433559/the-kcnh2-ivs9-28a-g-mutation-causes-aberrant-isoform-expression-and-herg-trafficking-defect-in-cardiomyocytes-derived-from-patients-affected-by-long-qt-syndrome-type-2
#4
Manuela Mura, Ashish Mehta, Chrishan J Ramachandra, Rita Zappatore, Federica Pisano, Maria Chiara Ciuffreda, Vincenzo Barbaccia, Lia Crotti, Peter J Schwartz, Winston Shim, Massimiliano Gnecchi
BACKGROUND: Long QT Syndrome type 2 (LQT2) is caused by mutations in the KCNH2 gene that encodes for the α-subunit (hERG) of the ion channel conducting the rapid delayed rectifier potassium current (IKr). We have previously identified a disease causing mutation (IVS9-28A/G) in the branch point of the splicing of KCNH2 intron 9. However, the mechanism through which this mutation causes the disease is unknown. METHODS AND RESULTS: We generated human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from fibroblasts of two IVS9-28A/G mutation carriers...
April 12, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28430892/anti-arrhythmic-potential-of-the-late-sodium-current-inhibitor-gs-458967-in-murine-scn5a-1798insd-and-human-scn5a-1795insd-ipsc-derived-cardiomyocytes
#5
Vincent Portero, Simona Casini, Maaike Hoekstra, Arie O Verkerk, Isabella Mengarelli, Luiz Belardinelli, Sridharan Rajamani, Arthur A M Wilde, Connie R Bezzina, Marieke W Veldkamp, Carol Ann Remme
AIM: Selective inhibition of cardiac late sodium current (INaL) is an emerging target in the treatment of ventricular arrhythmias. We investigated the electrophysiological effects of GS-458967 (GS967), a potent, selective inhibitor of INaL, in an overlap syndrome model of both gain and loss of sodium channel function, comprising cardiomyocytes derived from both human SCN5A-1795insD+/- induced pluripotent stem cells (hiPSC-CMs) and mice carrying the homologous mutation Scn5a-1798insD+/-...
April 18, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28421296/metabolite-signatures-of-doxorubicin-induced-toxicity-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#6
Umesh Chaudhari, James K Ellis, Vilas Wagh, Harshal Nemade, Jürgen Hescheler, Hector C Keun, Agapios Sachinidis
Drug-induced off-target cardiotoxicity, particularly following anti-cancer therapy, is a major concern in new drug discovery and development. To ensure patient safety and efficient pharmaceutical drug development, there is an urgent need to develop more predictive cell model systems and distinct toxicity signatures. In this study, we applied our previously proposed repeated exposure toxicity methodology and performed (1)H NMR spectroscopy-based extracellular metabolic profiling in culture medium of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exposed to doxorubicin (DOX), an anti-cancer agent...
April 18, 2017: Amino Acids
https://www.readbyqxmd.com/read/28421116/mitochondrial-maturation-in-human-pluripotent-stem-cell-derived-cardiomyocytes
#7
Dao-Fu Dai, Maria Elena Danoviz, Brian Wiczer, Michael A Laflamme, Rong Tian
Human pluripotent stem cells derived cardiomyocytes (PSC-CMs) have been widely used for disease modeling, drug safety screening, and preclinical cell therapy to regenerate myocardium. Most studies have utilized PSC-CM grown in vitro for a relatively short period after differentiation. These PSC-CMs demonstrated structural, electrophysiological, and mechanical features of primitive cardiomyocytes. A few studies have extended in vitro PSC-CM culture time and reported improved maturation of structural and electromechanical properties...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28420436/autophagy-mediates-the-beneficial-effect-of-hypoxic-preconditioning-on-bone-marrow-mesenchymal-stem-cells-for-the-therapy-of-myocardial-infarction
#8
Zheng Zhang, Chao Yang, Mingzhi Shen, Ming Yang, Zhitao Jin, Liping Ding, Wei Jiang, Junke Yang, Haixu Chen, Feng Cao, Taohong Hu
BACKGROUND: Stem cell therapy has emerged as a promising therapeutic strategy for myocardial infarction (MI). However, the poor viability of transplanted stem cells hampers their therapeutic efficacy. Hypoxic preconditioning (HPC) can effectively promote the survival of stem cells. The aim of this study was to investigate whether HPC improved the functional survival of bone marrow mesenchymal stem cells (BM-MSCs) and increased their cardiac protective effect. METHODS: BM-MSCs, isolated from Tg(Fluc-egfp) mice which constitutively express both firefly luciferase (Fluc) and enhanced green fluorescent protein (eGFP), were preconditioned with HPC (1% O2) for 12 h, 24 h, 36 h, and 48 h, respectively, followed by 24 h of hypoxia and serum deprivation (H/SD) injury...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28419336/ip3r-mediated-ca2-signals-govern-hematopoietic-and-cardiac-divergence-of-flk1-cells-via-the-calcineurin-nfatc3-etv2-pathway
#9
Yi-Jie Wang, Jijun Huang, Wenqiang Liu, Xiaochen Kou, Huayuan Tang, Hong Wang, Xiujian Yu, Shaorong Gao, Kunfu Ouyang, Huang-Tian Yang
Ca2+ signals participate in various cellular processes with spatial and temporal dynamics, among which, inositol 1,4,5-trisphosphate receptors (IP3Rs)-mediated Ca2+ signals are essential for early development. However, the underlying mechanisms of IP3R-regulated cell fate decision remain largely unknown. Here we report that IP3Rs are required for the hematopoietic and cardiac fate divergence of mouse embryonic stem cells (mESCs). Deletion of IP3Rs (IP3R-tKO) reduced Flk1+/PDGFRα- hematopoietic mesoderm, c-Kit+/CD41+ hematopoietic progenitor cell population, and the colony-forming unit activity, but increased cardiac progenitor markers as well as cardiomyocytes...
April 13, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28412246/absence-of-nucks-augments-paracrine-effects-of-mesenchymal-stem-cells-mediated-cardiac-protection
#10
Yuelin Zhang, Sinming Chiu, Xiaoting Liang, Yuet-Hung Chai, Yiming Qin, Junwen Wang, Xiang Li, Beiying Qiu, Vinay Tergaonkar, Hung-Fat Tse, Qizhou Lian
Bone marrow-derived mesenchymal stem cells (BM-MSCs) contribute to myocardial repair after myocardial infarction (MI) by secreting a panel of growth factors and cytokines. This study was to investigate the potential mechanisms of the nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS) in regulation of the profiles of BM-MSCs secretion and compare the therapeutic efficacy of NUCKS(-/-)- and wide type-BM-MSCs (WT-BM-MSCs) on MI. The secretion profiles between NUCKS(-/-)- and WT-BM-MSCs under hypoxia (1%O2) were analyzed...
April 12, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28410643/high-throughput-and-cost-effective-characterization-of-induced-pluripotent-stem-cells
#11
Matteo D'Antonio, Grace Woodruff, Jason L Nathanson, Agnieszka D'Antonio-Chronowska, Angelo Arias, Hiroko Matsui, Roy Williams, Cheryl Herrera, Sol M Reyna, Gene W Yeo, Lawrence S B Goldstein, Athanasia D Panopoulos, Kelly A Frazer
Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) offers the possibility of studying the molecular mechanisms underlying human diseases in cell types difficult to extract from living patients, such as neurons and cardiomyocytes. To date, studies have been published that use small panels of iPSC-derived cell lines to study monogenic diseases. However, to study complex diseases, where the genetic variation underlying the disorder is unknown, a sizable number of patient-specific iPSC lines and controls need to be generated...
April 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28410642/ipscore-a-resource-of-222-ipsc-lines-enabling-functional-characterization-of-genetic-variation-across-a-variety-of-cell-types
#12
Athanasia D Panopoulos, Matteo D'Antonio, Paola Benaglio, Roy Williams, Sherin I Hashem, Bernhard M Schuldt, Christopher DeBoever, Angelo D Arias, Melvin Garcia, Bradley C Nelson, Olivier Harismendy, David A Jakubosky, Margaret K R Donovan, William W Greenwald, KathyJean Farnam, Megan Cook, Victor Borja, Carl A Miller, Jonathan D Grinstein, Frauke Drees, Jonathan Okubo, Kenneth E Diffenderfer, Yuriko Hishida, Veronica Modesto, Carl T Dargitz, Rachel Feiring, Chang Zhao, Aitor Aguirre, Thomas J McGarry, Hiroko Matsui, He Li, Joaquin Reyna, Fangwen Rao, Daniel T O'Connor, Gene W Yeo, Sylvia M Evans, Neil C Chi, Kristen Jepsen, Naoki Nariai, Franz-Josef Müller, Lawrence S B Goldstein, Juan Carlos Izpisua Belmonte, Eric Adler, Jeanne F Loring, W Travis Berggren, Agnieszka D'Antonio-Chronowska, Erin N Smith, Kelly A Frazer
Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection of systematically derived and characterized iPSC lines from 222 ethnically diverse individuals that allows for both familial and association-based genetic studies. iPSCORE lines are pluripotent with high genomic integrity (no or low numbers of somatic copy-number variants) as determined using high-throughput RNA-sequencing and genotyping arrays, respectively...
April 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28410244/platelet-derived-growth-factor-receptor-alpha-positive-cardiac-progenitor-cells-derived-from-multipotent-germline-stem-cells-are-capable-of-cardiomyogenesis-in-vitro-and-in-vivo
#13
Bang-Jin Kim, Yong-Hee Kim, Yong-An Lee, Sang-Eun Jung, Yeong Ho Hong, Eun-Ju Lee, Byung-Gak Kim, Seongsoo Hwang, Jeong Tae Do, Myung-Geol Pang, Buom-Yong Ryu
Cardiac cell therapy has the potential to revolutionize treatment of heart diseases, but its success hinders on the development of a stem cell therapy capable of efficiently producing functionally differentiated cardiomyocytes. A key to unlocking the therapeutic application of stem cells lies in understanding the molecular mechanisms that govern the differentiation process. Here we report that a population of platelet-derived growth factor receptor alpha (PDGFRA) cells derived from mouse multipotent germline stem cells (mGSCs) were capable of undergoing cardiomyogenesis in vitro...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408211/cardiac-voltage-gated-ion-channels-in-safety-pharmacology-review-of-the-landscape-leading-to-the-cipa-initiative
#14
REVIEW
Hai Huang, Michael K Pugsley, Bernard Fermini, Michael J Curtis, John Koerner, Michael Accardi, Simon Authier
Voltage gated ion channels are central in defining the fundamental properties of the ventricular cardiac action potential (AP), and are also involved in the development of drug-induced arrhythmias. Many drugs can inhibit cardiac ion currents, including the Na(+) current (INa), L-type Ca(2+) current (Ica-L), and K(+) currents (Ito, IK1, IKs, and IKr), and thereby affect AP properties in a manner that can trigger or sustain cardiac arrhythmias. Since publication of ICH E14 and S7B over a decade ago, there has been a focus on drug effects on QT prolongation clinically, and on the rapidly activating delayed rectifier current (IKr), nonclinically, for evaluation of proarrhythmic risk...
April 11, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28404615/myeloperoxidase-mediates-postischemic-arrhythmogenic-ventricular-remodeling
#15
Martin Mollenhauer, Kai Friedrichs, Max Lange, Jan Gesenberg, Lisa Remane, Christina Kerkenpaß, Jenny Krause, Johanna Schneider, Thorben Ravekes, Martina Maass, Marcel Halbach, Gabriel Peinkofer, Tomo Saric, Dennis Mehrkens, Matti Adam, Florian G Deuschl, Denise Lau, Birgit Geertz, Kashish Manchanda, Thomas Eschenhagen, Lukas Kubala, Tanja K Rudolph, Yuping Wu, Wh W Tang, Stanley L Hazen, Stephan Baldus, Anna Klinke, Volker Rudolph
Rationale: Ventricular arrhythmias remain the leading cause of death in patients suffering myocardial ischemia. Myeloperoxidase (MPO), a heme-enzyme released by polymorphonuclear neutrophils, accumulates within ischemic myocardium and has been linked to adverse left ventricular remodeling. Objective: To reveal the role of MPO for the development of ventricular arrhythmias. Methods and Results: In different murine models of myocardial ischemia MPO deficiency profoundly decreased vulnerability for ventricular tachycardia (VT) upon programmed right ventricular and burst stimulation and spontaneously as assessed by ECG telemetry following isoproterenol injection...
April 12, 2017: Circulation Research
https://www.readbyqxmd.com/read/28397099/maturation-of-human-pluripotent-stem-cell-derived-cardiomyocytes-is-improved-in-cardiovascular-construct
#16
Hanna Vuorenpää, Kirsi Penttinen, Tuula Heinonen, Mari Pekkanen-Mattila, Jertta-Riina Sarkanen, Timo Ylikomi, Katriina Aalto-Setälä
In order to translate preclinical data into the clinical studies, relevant in vitro models with structure and key functional properties similar to native human tissue should be used. In vitro cardiac models with vascular structures mimic the highly vascularized myocardium and provide interactions between endothelial cells, stromal cells and cardiomyocytes. Currently, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have been shown to present immature morphology and fetal-like electrophysiological properties that may limit their use as physiological test platform...
April 10, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28396709/human-ipsc-derived-myocardium-on-chip-with-capillary-like-flow-for-personalized-medicine
#17
Bradley W Ellis, Aylin Acun, U Isik Can, Pinar Zorlutuna
The heart wall tissue, or the myocardium, is one of the main targets in cardiovascular disease prevention and treatment. Animal models have not been sufficient in mimicking the human myocardium as evident by the very low clinical translation rates of cardiovascular drugs. Additionally, current in vitro models of the human myocardium possess several shortcomings such as lack of physiologically relevant co-culture of myocardial cells, lack of a 3D biomimetic environment, and the use of non-human cells. In this study, we address these shortcomings through the design and manufacture of a myocardium-on-chip (MOC) using 3D cell-laden hydrogel constructs and human induced pluripotent stem cell (hiPSC) derived myocardial cells...
March 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/28396518/rapamycin-efficiently-promotes-cardiac-differentiation-of-mouse-embryonic-stem-cells
#18
Qin Lu, Zhuqing Jia, Yang Wang, Weiping Wang, Zhe Yang, Tao Li, Yuyao Tian, Ping Chen, Kangtao Ma, Yinan Liu, Chunyan Zhou
To investigate the effects of the rapamycin on cardiac differentiation, murine ESCs was induced to cardiomyocytes by 10(-4) M ascorbic acid (AA), 20 nM rapamycin alone or 0.1‰ solvent dimethyl sulfoxide (DMSO). We found that rapamycin alone was insufficient to initiate cardiomyogenesis. Then the ESCs was treated with AA and rapamycin (20 nM) or AA and DMSO (0.1‰) as a control. Compared with control, mESCs treated with rapamycin (20 nM) and AA yielded a significantly higher percentage of cardiomyocytes, as confirmed by percentage of beating EBs, the immunofluorescence and FACS analysis...
April 10, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28392217/high-throughput-and-cost-effective-characterization-of-induced-pluripotent-stem-cells
#19
Matteo D'Antonio, Grace Woodruff, Jason L Nathanson, Agnieszka D'Antonio-Chronowska, Angelo Arias, Hiroko Matsui, Roy Williams, Cheryl Herrera, Sol M Reyna, Gene W Yeo, Lawrence S B Goldstein, Athanasia D Panopoulos, Kelly A Frazer
Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) offers the possibility of studying the molecular mechanisms underlying human diseases in cell types difficult to extract from living patients, such as neurons and cardiomyocytes. To date, studies have been published that use small panels of iPSC-derived cell lines to study monogenic diseases. However, to study complex diseases, where the genetic variation underlying the disorder is unknown, a sizable number of patient-specific iPSC lines and controls need to be generated...
April 4, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28392216/ipscore-a-resource-of-222-ipsc-lines-enabling-functional-characterization-of-genetic-variation-across-a-variety-of-cell-types
#20
Athanasia D Panopoulos, Matteo D'Antonio, Paola Benaglio, Roy Williams, Sherin I Hashem, Bernhard M Schuldt, Christopher DeBoever, Angelo D Arias, Melvin Garcia, Bradley C Nelson, Olivier Harismendy, David A Jakubosky, Margaret K R Donovan, William W Greenwald, KathyJean Farnam, Megan Cook, Victor Borja, Carl A Miller, Jonathan D Grinstein, Frauke Drees, Jonathan Okubo, Kenneth E Diffenderfer, Yuriko Hishida, Veronica Modesto, Carl T Dargitz, Rachel Feiring, Chang Zhao, Aitor Aguirre, Thomas J McGarry, Hiroko Matsui, He Li, Joaquin Reyna, Fangwen Rao, Daniel T O'Connor, Gene W Yeo, Sylvia M Evans, Neil C Chi, Kristen Jepsen, Naoki Nariai, Franz-Josef Müller, Lawrence S B Goldstein, Juan Carlos Izpisua Belmonte, Eric Adler, Jeanne F Loring, W Travis Berggren, Agnieszka D'Antonio-Chronowska, Erin N Smith, Kelly A Frazer
Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection of systematically derived and characterized iPSC lines from 222 ethnically diverse individuals that allows for both familial and association-based genetic studies. iPSCORE lines are pluripotent with high genomic integrity (no or low numbers of somatic copy-number variants) as determined using high-throughput RNA-sequencing and genotyping arrays, respectively...
April 3, 2017: Stem Cell Reports
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