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November 2012

Wei H, Zhang G, Qiu S, Lu J, Sheng J, Manasi, Tan G, Wong P, Gan SU, and Shim W

Hydrogen Sulfide Suppresses Outward Rectifier Potassium Currents in Human Pluripotent Stem Cell-derived Cardiomyocytes

PLoS One 7(11):e50641

Publication Date: November 30, 2012

Product Type: iCell Cardiomyocytes

Summary:

Hydrogen sulfide (H2S) is a potential cardioprotective agent of unknown mechanism. This study demonstrates the effect of H2S on the cardiac action potential and ionic currents.

Impact:

iCell Cardiomyocytes and their functionality enabled confirmation of known effects and delucidation of novel effects of H2S.

September 2012

Puppala D, Collis LP, Sun SZ, Bonato V, Chen X, Anson B, Pletcher M, Fermini B, and Engle SJ

Comparative Gene Expression Profiling in Human Induced Pluripotent Stem Cell-derived Cardiocytes and Human and Cynomolgus Heart

Toxicol Sci 131(1):292-301

Publication Date: September 14, 2012

Product Type: iCell Cardiomyocytes

Summary:

Gene expression analysis of iCell Cardiomyocytes over a period of 42 days in culture post-thaw and comparison to human fetal and adult cardiac tissue as well as non-human primate cardiac tissue. iCell Cardiomyocytes contractility exhibited functional and pharmacological correlation with myocytes isolated from adult non-human primate heart tissue.

Impact:

This study demonstrated that iCell Cardiomyocytes exhibit genomic signatures similar to adult human heart cells and functional characteristics that correlate with non-human primate heart tissue and thus represent a relevant human model to assess cardiac function.

Sirenko O, Critteden C, Callamaras N, Hesley J, Chen YW, Funes C, Rusyn I, Anson B, and Cromwell EF

Multiparameter In Vitro Assessment of Compound Effects on Cardiomyocyte Physiology Using iPS Cells

J Biomol Screen 18(1):39-53

Publication Date: September 12, 2012

Product Type: iCell Cardiomyocytes

Summary:

The FLIPR Tetra High Throughput Cellular Screening System was used to assess cardiac cell physiology and the effects of small molecules on iCell Cardiomyocytes function.

Impact:

This study demonstrated that iCell Cardiomyocytes can be used to assess the effects of small molecules on cardiac function using a high throughput screening platform commonly used in pharmaceutical drug safety and efficacy testing.

August 2012

Cerignoli F, Charlot D, Whittaker R, Ingermanson R, Gehalot P, Savchenko A, Gallacher DJ, Towart R, Price JH, McDonough PM, and Mercola M

High Throughput Measurement of Ca2+ Dynamics for Drug Risk Assessment in Human Stem Cell-derived Cardiomyocytes by Kinetic Image Cytometry

J Pharmacol Toxicol Methods 66(3):246-56

Publication Date: August 25, 2012

Product Type: iCell Cardiomyocytes

Summary:

iCell Cardiomyocytes were treated with known cardiotoxic and arrhythmogenic drugs and kinetically analyzed for intracellular calcium concentration ([Ca2+]i). A novel kinetic imaging cytometry (KIC) platform was used to achieve automated, high-resolution, and high-throughput single cell measurement of intracellular fluorescent Ca2+ indicators.

Impact:

iCell Cardiomyocytes showed appropriate biochemical responses to known toxic drug compounds in a high-throughput assay. Data support the use of iCell Cardiomyocytes as a relevant human model system that can be applied in an automated, high-throughput workflow to predict drug-induced cardiotoxicity.

Mioulane M, Foldes G, Ali NN, Schneider MD, and Harding SE

Development of High Content Imaging Methods for Cell Death Detection in Human Pluripotent Stem Cell-derived Cardiomyocytes

J Cardiovasc Transl Res 5(5):593-604

Publication Date: August 16, 2012

Product Type: iCell Cardiomyocytes

Summary:

iCell Cardiomyocytes were used in a novel, simple, automated, and scalable fluorescent microscopy assay system to simultaneously measure multiple biochemical endpoints including nuclear remodeling, mitochondrial function, apoptosis, and necrosis.

Impact:

This study demonstrated the use of iCell Cardiomyocytes to assess the effects of drug compounds on multiple cardiac biochemical pathways using an automated high content platform commonly used in the pharmaceutical industry.

June 2012

Rana P, Anson B, Engle S, and Will Y

Characterization of Human-induced Pluripotent Stem Cell-derived Cardiomyocytes: Bioenergetics and Utilization in Safety Screening

Toxicol Sci 130(1):117-31

Publication Date: June 27, 2012

Product Type: iCell Cardiomyocytes

Summary:

Analysis of iCell Cardiomyocytes bioenergetics function revealed that iCell Cardiomyocytes can utilize a variety of energy substrates and exhibit expected responses to known mitochondrial toxicants.

Impact:

iCell Cardiomyocytes were shown to exhibit appropriate bioenergetics functions and can be used to detect mitochondrial dysfunction, which is an important mechanism of drug-induced cardiotoxicity.

Zhi D, Irvin MR, Gu CC, Stoddard AJ, Lorier R, Matter A, Rao DC, Srinivasasainagendra V, Tiwari HK, Turner A, Broeckel U, and Arnett DK

Whole-exome Sequencing and an iPSC-derived Cardiomyocyte Model Provides a Powerful Platform for Gene Discovery in Left Ventricular Hypertrophy

Front Genet 3:92

Publication Date: June 2, 2012

Product Type: iCell Cardiomyocytes

Summary:

iCell Cardiomyocytes were used to develop a functional cellular model of left ventricular hypertrophy (LVH), which enabled the identification of novel disease-associated genetic polymorphisms from a donor population.

Impact:

iCell Cardiomyocytes were used to develop an in vitro cellular model that exhibits functional characteristics of the human cardiac disease LVH. This model was used to identify novel genetic markers associated with the disease.

May 2012

Lee P, Klos M, Bollensdorff C, Hou L, Ewart P, Kamp TJ, Zhang J, Bizy A, Guerrero-Serna G, Kohl P, Jalife J, and Herron TJ

Simultaneous Voltage and Calcium Mapping of Genetically Purified Human Induced Pluripotent Stem Cell-derived Cardiac Myocyte Monolayers

Circ Res 110(12):1556-63

Publication Date: May 8, 2012

Product Type: iCell Cardiomyocytes

Summary:

iCell Cardiomyocytes were used to study mechanisms of cardiac arrhythmia using a multiparametric imaging system that simultaneously measures action potential and intracellular calcium wave propagation.

Impact:

This study demonstrated that iCell Cardiomyocytes can be used in a novel high-throughput assay system to assess drug effects on cardiac arrhythmias. Data showed that iCell Cardiomyocytes offer advantages over commonly used rodent models.

April 2012

Reynolds JG, Geretti E, Hendriks BS, Lee H, Leonard SC, Klinz SG, Noble CO, Lücker PB, Zandstra PW, Drummond DC, Olivier KJ Jr, Nielsen UB, Niyikiza C, Agresta SV, and Wickham TJ

HER2-targeted Liposomal Doxorubicin Displays Enhanced Anti-tumorigenic Effects without Associated Cardiotoxicity

Toxicol Appl Pharmacol 262(1):1-10

Publication Date: April 21, 2012

Product Type: iCell Cardiomyocytes

Summary:

iCell Cardiomyocytes were used to support the assertion that HER-2 targeted liposomal doxorubicin does not induce cardiotoxicity. Data were included in an Investigational New Drug (IND) application submitted to the FDA.

Impact:

iCell Cardiomyocytes provided a relevant human model system to advance a new drug candidate through the drug development pipeline. This is the first known instance of data generated using an iPS cell-derived model being used to support an IND filing to the FDA.

January 2012

Babiarz JE, Ravon M, Sridhar S, Ravindran P, Swanson B, Bitter H, Weiser T, Chiao E, Certa U, and Kolaja KL

Determination of the Human Cardiomyocyte mRNA and miRNA Differentiation Network by Fine-scale Profiling

Stem Cells Dev 21(11):1956-65

Publication Date: January 4, 2012

Product Type: iCell Cardiomyocytes

Summary:

iCell Cardiomyocytes mRNA and miRNA transcriptomes were analyzed at various time-points during and post-differentiation and compared to primary cardiac tissue biopsied from human fetal, adult normal and hypertensive hearts.

Impact:

This study demonstrated that iCell Cardiomyocytes exhibit developmental markers similar to native human cardiac tissue and maintain a stable cardiac cell phenotype for several months in culture. Data support the use of iCell Cardiomyocytes as a relevant human model system for both acute and chronic studies of cardiac cell function.

November 2011

Jonsson MK, Wang QD, and Becker B

Impedance-based Detection of Beating Rhythm and Proarrhythmic Effects of Compounds on Stem Cell-derived Cardiomyocytes

Assay Drug Dev Technol 9(6):589-99

Publication Date: November 15, 2011

Product Type: iCell Cardiomyocytes

Summary:

A series of reference compounds were used to demonstrate the use of iCell Cardiomyocytes with the xCELLigence RTCA Cardio System to detect compound effects on cardiac beat frequency and arrhythmias over an assay period of several days.

Impact:

iCell Cardiomyocytes exhibit electrophysiological characteristics similar to native human cardiomyocytes and showed appropriate response to known toxic drug compounds using a cell analysis platform commonly used in the pharmaceutical industry.

September 2011

Ma J, Guo L, Fiene SJ, Anson BD, Thomson JA, Kamp TJ, Kolaja KL, Swanson BJ, and January CT

High Purity Human-induced Pluripotent Stem Cell-derived Cardiomyocytes: Electrophysiological Properties of Action Potentials and Ionic Currents

Am J Physiol Heart Circ Physiol 301(5):H2006-17

Publication Date: September 2, 2011

Product Type: iCell Cardiomyocytes

Summary:

This comprehensive characterization study demonstrated that iCell Cardiomyocytes display cellular electrophysiological properties similar to native human cardiomyocytes.

Impact:

iCell Cardiomyocytes exhibit electrophysiological characteristics similar to native human cardiomyocytes and thus provide a relevant in vitro model for disease modeling, drug discovery, and toxicity testing.

August 2011

Cohen JD, Babiarz JE, Abrams RM, Guo L, Kameoka S, Chiao E, Taunton J, and Kolaja KL

Use of Human Stem Cell-derived Cardiomyocytes to Examine Sunitinib Mediated Cardiotoxicity and Electrophysiological Alterations

Toxicol Appl Pharmacol 257(1):74-83

Publication Date: August 27, 2011

Product Type: iCell Cardiomyocytes

Summary:

Elucidation of the molecular mechanisms of sunitinib-induced cardiotoxicity using iCell Cardiomyocytes revealed, contrary to previous data using rodent models, that AMPK and RSK do not play a significant role.

Impact:

This study illustrates the limitations of non-human model systems and the benefit and importance of using a human cell-based model system to detect and study human cardiotoxicity.

June 2011

Guo L, Abrams RM, Babiarz JE, Cohen JD, Kameoka S, Sanders MJ, Chiao E, and Kolaja KL

Estimating the Risk of Drug-induced Proarrhythmia Using Human Induced Pluripotent Stem Cell-derived Cardiomyocytes

Toxicol Sci 123(1):281-9

Publication Date: June 20, 2011

Product Type: iCell Cardiomyocytes

Summary:

Analysis of 28 compounds with known cardiac effects was performed using iCell Cardiomyocytes and the xCELLigence RTCA Cardio System. Compound-specific changes in cardiac beat rate and/or the amplitude of the impedance measurement were consistent with clinical findings. The results were confirmed using iCell Cardiomyocytes and a multielectrode array (MEA) platform.

Impact:

iCell Cardiomyocytes responded to known cardiotoxic compounds in a manner consistent with clinical observations. Analysis was performed using two cell analysis platforms commonly used in the pharmaceutical industry.

Guo L, Qian JY, Abrams R, Tang HM, Weiser T, Sanders MJ, and Kolaja KL

The Electrophysiological Effects of Cardiac Glycosides in Human iPSC-derived Cardiomyocytes and in Guinea Pig Isolated Hearts

Cell Physiol Biochem 27(5):453-62

Publication Date: June 15, 2011

Product Type: iCell Cardiomyocytes

Summary:

Pharmacological and toxicological effects of cardiac glycosides (ouabain, digoxin) and the L-type Ca2+ channel antagonist nifedipine were measured in iCell Cardiomyocytes using a multielectrode array (MEA) platform. The observed changes in field potential duration and Ca2+ wave amplitude correlated with the compounds’ effects on QT interval and contractility in guinea pig Langendorff hearts.

Impact:

iCell Cardiomyocytes showed expected pharmacological and toxicological responses to compounds known to disrupt cardiac cell function through a variety of biochemical mechanisms

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