The Experts below are selected from a list of 14316 Experts worldwide ranked by ideXlab platform
Ping Liang - One of the best experts on this subject based on the ideXlab platform.
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screening drug induced Arrhythmia events using human induced pluripotent stem cell derived cardiomyocytes and low impedance microelectrode arrays
Circulation, 2013Co-Authors: Enrique G Navarrete, Ping Liang, Veronica Sanchezfreire, Chelsey S Simmons, Tingyu Gong, Arun Sharma, Paul W Burridge, Bhagat Patlolla, Haodi Wu, Ramin E BeyguiAbstract:Background—Drug-Induced Arrhythmia is one of the most common causes of drug development failure and withdrawal from market. This study tested whether human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) combined with a low-impedance microelectrode array (MEA) system could improve on industry-standard preclinical cardiotoxicity screening methods, identify the effects of well-characterized drugs, and elucidate underlying risk factors for Drug-Induced Arrhythmia. hiPSC-CMs may be advantageous over immortalized cell lines because they possess similar functional characteristics as primary human cardiomyocytes and can be generated in unlimited quantities. Methods and Results—Pharmacological responses of beating embryoid bodies exposed to a comprehensive panel of drugs at 65 to 95 days postinduction were determined. Responses of hiPSC-CMs to drugs were qualitatively and quantitatively consistent with the reported drug effects in literature. Torsadogenic hERG blockers, such as sotalol and quinid...
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drug screening using a library of human induced pluripotent stem cell derived cardiomyocytes reveals disease specific patterns of cardiotoxicity
Circulation, 2013Co-Authors: Ping Liang, Veronica Sanchezfreire, Tingyu Gong, Yongming Wang, Sebastian Diecke, Karim Sallam, Joshua W Knowles, Paul J Wang, Patricia K Nguyen, Donald M BersAbstract:Background—Cardiotoxicity is a leading cause for drug attrition during pharmaceutical development and has resulted in numerous preventable patient deaths. Incidents of adverse cardiac drug reactions are more common in patients with preexisting heart disease than the general population. Here we generated a library of human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) from patients with various hereditary cardiac disorders to model differences in cardiac drug toxicity susceptibility for patients of different genetic backgrounds. Methods and Results—Action potential duration and Drug-Induced Arrhythmia were measured at the single cell level in hiPSC-CMs derived from healthy subjects and patients with hereditary long QT syndrome, familial hypertrophic cardiomyopathy, and familial dilated cardiomyopathy. Disease phenotypes were verified in long QT syndrome, hypertrophic cardiomyopathy, and dilated cardiomyopathy hiPSC-CMs by immunostaining and single cell patch clamp. Human embryonic stem c...
Hong Shi - One of the best experts on this subject based on the ideXlab platform.
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international multisite study of human induced pluripotent stem cell derived cardiomyocytes for drug proarrhythmic potential assessment
Cell Reports, 2018Co-Authors: Ksenia Blinova, Qianyu Dang, Daniel C Millard, Godfrey L Smith, Jennifer Pierson, Liang Guo, Mathew Brock, Udo Kraushaar, Haoyu Zeng, Hong ShiAbstract:To assess the utility of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as an in vitro proArrhythmia model, we evaluated the concentration dependence and sources of variability of electrophysiologic responses to 28 drugs linked to low, intermediate, and high torsades de pointes (TdP) risk categories using two commercial cell lines and standardized protocols in a blinded multisite study using multielectrode array or voltage-sensing optical approaches. Logistical and ordinal linear regression models were constructed using drug responses as predictors and TdP risk categories as outcomes. Three of seven predictors (Drug-Induced Arrhythmia-like events and prolongation of repolarization at either maximum tested or maximal clinical exposures) categorized drugs with reasonable accuracy (area under the curve values of receiver operator curves ∼0.8). hiPSC-CM line, test site, and platform had minimal influence on drug categorization. These results demonstrate the utility of hiPSC-CMs to detect Drug-Induced proarrhythmic effects as part of the evolving Comprehensive In Vitro ProArrhythmia Assay paradigm.
Veronica Sanchezfreire - One of the best experts on this subject based on the ideXlab platform.
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screening drug induced Arrhythmia events using human induced pluripotent stem cell derived cardiomyocytes and low impedance microelectrode arrays
Circulation, 2013Co-Authors: Enrique G Navarrete, Ping Liang, Veronica Sanchezfreire, Chelsey S Simmons, Tingyu Gong, Arun Sharma, Paul W Burridge, Bhagat Patlolla, Haodi Wu, Ramin E BeyguiAbstract:Background—Drug-Induced Arrhythmia is one of the most common causes of drug development failure and withdrawal from market. This study tested whether human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) combined with a low-impedance microelectrode array (MEA) system could improve on industry-standard preclinical cardiotoxicity screening methods, identify the effects of well-characterized drugs, and elucidate underlying risk factors for Drug-Induced Arrhythmia. hiPSC-CMs may be advantageous over immortalized cell lines because they possess similar functional characteristics as primary human cardiomyocytes and can be generated in unlimited quantities. Methods and Results—Pharmacological responses of beating embryoid bodies exposed to a comprehensive panel of drugs at 65 to 95 days postinduction were determined. Responses of hiPSC-CMs to drugs were qualitatively and quantitatively consistent with the reported drug effects in literature. Torsadogenic hERG blockers, such as sotalol and quinid...
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drug screening using a library of human induced pluripotent stem cell derived cardiomyocytes reveals disease specific patterns of cardiotoxicity
Circulation, 2013Co-Authors: Ping Liang, Veronica Sanchezfreire, Tingyu Gong, Yongming Wang, Sebastian Diecke, Karim Sallam, Joshua W Knowles, Paul J Wang, Patricia K Nguyen, Donald M BersAbstract:Background—Cardiotoxicity is a leading cause for drug attrition during pharmaceutical development and has resulted in numerous preventable patient deaths. Incidents of adverse cardiac drug reactions are more common in patients with preexisting heart disease than the general population. Here we generated a library of human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) from patients with various hereditary cardiac disorders to model differences in cardiac drug toxicity susceptibility for patients of different genetic backgrounds. Methods and Results—Action potential duration and Drug-Induced Arrhythmia were measured at the single cell level in hiPSC-CMs derived from healthy subjects and patients with hereditary long QT syndrome, familial hypertrophic cardiomyopathy, and familial dilated cardiomyopathy. Disease phenotypes were verified in long QT syndrome, hypertrophic cardiomyopathy, and dilated cardiomyopathy hiPSC-CMs by immunostaining and single cell patch clamp. Human embryonic stem c...
Tingyu Gong - One of the best experts on this subject based on the ideXlab platform.
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screening drug induced Arrhythmia events using human induced pluripotent stem cell derived cardiomyocytes and low impedance microelectrode arrays
Circulation, 2013Co-Authors: Enrique G Navarrete, Ping Liang, Veronica Sanchezfreire, Chelsey S Simmons, Tingyu Gong, Arun Sharma, Paul W Burridge, Bhagat Patlolla, Haodi Wu, Ramin E BeyguiAbstract:Background—Drug-Induced Arrhythmia is one of the most common causes of drug development failure and withdrawal from market. This study tested whether human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) combined with a low-impedance microelectrode array (MEA) system could improve on industry-standard preclinical cardiotoxicity screening methods, identify the effects of well-characterized drugs, and elucidate underlying risk factors for Drug-Induced Arrhythmia. hiPSC-CMs may be advantageous over immortalized cell lines because they possess similar functional characteristics as primary human cardiomyocytes and can be generated in unlimited quantities. Methods and Results—Pharmacological responses of beating embryoid bodies exposed to a comprehensive panel of drugs at 65 to 95 days postinduction were determined. Responses of hiPSC-CMs to drugs were qualitatively and quantitatively consistent with the reported drug effects in literature. Torsadogenic hERG blockers, such as sotalol and quinid...
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drug screening using a library of human induced pluripotent stem cell derived cardiomyocytes reveals disease specific patterns of cardiotoxicity
Circulation, 2013Co-Authors: Ping Liang, Veronica Sanchezfreire, Tingyu Gong, Yongming Wang, Sebastian Diecke, Karim Sallam, Joshua W Knowles, Paul J Wang, Patricia K Nguyen, Donald M BersAbstract:Background—Cardiotoxicity is a leading cause for drug attrition during pharmaceutical development and has resulted in numerous preventable patient deaths. Incidents of adverse cardiac drug reactions are more common in patients with preexisting heart disease than the general population. Here we generated a library of human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) from patients with various hereditary cardiac disorders to model differences in cardiac drug toxicity susceptibility for patients of different genetic backgrounds. Methods and Results—Action potential duration and Drug-Induced Arrhythmia were measured at the single cell level in hiPSC-CMs derived from healthy subjects and patients with hereditary long QT syndrome, familial hypertrophic cardiomyopathy, and familial dilated cardiomyopathy. Disease phenotypes were verified in long QT syndrome, hypertrophic cardiomyopathy, and dilated cardiomyopathy hiPSC-CMs by immunostaining and single cell patch clamp. Human embryonic stem c...
Ksenia Blinova - One of the best experts on this subject based on the ideXlab platform.
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international multisite study of human induced pluripotent stem cell derived cardiomyocytes for drug proarrhythmic potential assessment
Cell Reports, 2018Co-Authors: Ksenia Blinova, Qianyu Dang, Daniel C Millard, Godfrey L Smith, Jennifer Pierson, Liang Guo, Mathew Brock, Udo Kraushaar, Haoyu Zeng, Hong ShiAbstract:To assess the utility of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as an in vitro proArrhythmia model, we evaluated the concentration dependence and sources of variability of electrophysiologic responses to 28 drugs linked to low, intermediate, and high torsades de pointes (TdP) risk categories using two commercial cell lines and standardized protocols in a blinded multisite study using multielectrode array or voltage-sensing optical approaches. Logistical and ordinal linear regression models were constructed using drug responses as predictors and TdP risk categories as outcomes. Three of seven predictors (Drug-Induced Arrhythmia-like events and prolongation of repolarization at either maximum tested or maximal clinical exposures) categorized drugs with reasonable accuracy (area under the curve values of receiver operator curves ∼0.8). hiPSC-CM line, test site, and platform had minimal influence on drug categorization. These results demonstrate the utility of hiPSC-CMs to detect Drug-Induced proarrhythmic effects as part of the evolving Comprehensive In Vitro ProArrhythmia Assay paradigm.
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International Multisite Study of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Drug Proarrhythmic Potential Assessment
Elsevier, 2018Co-Authors: Ksenia Blinova, Qianyu Dang, Jennifer Pierson, Liang Guo, Mathew Brock, Udo Kraushaar, Daniel Millard, Godfrey Smith, Haoyu ZengAbstract:Summary: To assess the utility of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as an in vitro proArrhythmia model, we evaluated the concentration dependence and sources of variability of electrophysiologic responses to 28 drugs linked to low, intermediate, and high torsades de pointes (TdP) risk categories using two commercial cell lines and standardized protocols in a blinded multisite study using multielectrode array or voltage-sensing optical approaches. Logistical and ordinal linear regression models were constructed using drug responses as predictors and TdP risk categories as outcomes. Three of seven predictors (Drug-Induced Arrhythmia-like events and prolongation of repolarization at either maximum tested or maximal clinical exposures) categorized drugs with reasonable accuracy (area under the curve values of receiver operator curves ∼0.8). hiPSC-CM line, test site, and platform had minimal influence on drug categorization. These results demonstrate the utility of hiPSC-CMs to detect Drug-Induced proarrhythmic effects as part of the evolving Comprehensive In Vitro ProArrhythmia Assay paradigm. : Blinova et al. tested human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for improving torsades de pointes Arrhythmia risk prediction of drugs in the Comprehensive In Vitro ProArrhythmia Assay (CiPA) initiative. This validation study confirms their utility based on electrophysiologic responses to 28 blinded drugs, with minimal influence from cell lines, test sites, and electrophysiological platforms. Keywords: comprehensive in vitro proArrhythmia assay, CiPA, human-induced pluripotent stem cell-derived cardiomycotes, hiPSC-CM, Drug-Induced ventricular Arrhythmia Torsade de Pointes, microelectrode array, voltage-sensitive dye
