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December 2012

Xu X, Lei Y, Luo J, Wang J, Zhang S, Yang XJ, Sun M, Nuwaysir E, Fan G, Zhao J, Lei L, and Zhong Z

Prevention of ß-amyloid Induced Toxicity in Human iPS Cell-derived Neurons by Inhibition of Cyclin-dependent Kinases and Associated Cell Cycle Events

Stem Cell Res 10(2):213-27

Publication Date: December 7, 2012

Product Type: iCell GABANeurons

Summary:

iCell Neurons were used to develop a novel, robust, and sensitive Aß toxicity-mediated model of Alzheimer’s disease, which was subsequently used in a screen of several hundred compounds from a proprietary GlaxoSmithKline compound library. Nineteen hits were identified, and one hit, a Cdk2 inhibitor, was selected for a follow up study using iCell Neurons to confirm the mechanism of action.

Impact:

iCell Neurons were successfully used to model Alzheimer’s disease and employed in a high-throughput small molecule screen for modulators of the disease phenotype. This is the first known example of iPS cell-derived neurons used in an Aß toxicity screen and demonstrates the use of iCell Neurons for disease modeling and drug screening for neurodegenerative disease.

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

Maloney JA, Bainbridge T, Gustafson A, Zhang S, Kyauk R, Steiner P, van der Brug M, Liu Y, Ernst JA, Watts RJ, and Atwal JK

Molecular Mechanisms of Alzheimer’s Disease Protection by the A673T Allele of the Amyloid Precursor Protein

J Biol Chem. 289(45):30990-1000

Publication Date: September 24, 2012

Summary:

MyCell Neurons were used to investigate the impact of SNPs in the amyloid precursor protein as it relates to Alzheimer’s disease (AD) progression.

Impact:

MyCell Neurons, cortical neurons manufactured from Alzheimer’s disease model iPS cell lines for this study, express the AD-related amyloid precursor protein making them useful for studying disease behavior and enabling therapeutics research.

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.

Haythornthwaite A, Stoelzle S, Hasler A, Kiss A, Mosbacher J, George M, Brüggemann A, and Fertig N

Characterizing Human Ion Channels in Induced Pluripotent Stem Cell-derived Neurons

J Biomol Screen 17(9):1264-72

Publication Date: August 24, 2012

Product Type: iCell GABANeurons

Summary:

This characterization study demonstrated that iCell Neurons display cellular electrophysiological properties similar to native human neurons using manual and automated patch clamp recordings.

Impact:

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

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.

Chai X, Dage JL, and Citron M

Constitutive Secretion of Tau Protein by an Unconventional Mechanism

Neurobiol Dis 48(3):356-66

Publication Date: June 2, 2012

Product Type: iCell GABANeurons

Summary:

This study was designed to elucidate the mechanism(s) of tau processing and cellular trafficking, the dysregulation of which is a hallmark of Alzheimer’s disease and other tauopathies. iCell Neurons were shown to release a small percentage of intracellular tau by a nonconventional pathway that correlates with tau levels observed in vivo.

Impact:

iCell Neurons provided a biologically relevant human cell model to study the protein tau, which plays an important role in the development of Alzheimer’s disease and other neurodegenerative disorders. iCell Neurons provided significant advantages over other available model systems including transformed cell lines and primary neurons in intact animals.

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.

Phillips MJ, Wallace KA, Dickerson SJ, Miller MJ, Verhoeven AD, Martin JM, Wright LS, Shen W, Capowski EE, Percin EF, Perez ET, Zhong X, Canto-Soler MV, and Gamm DM

Blood-derived Human iPS Cells Generate Optic Vesicle-like Structures with the Capacity to Form Retinal Laminae and Develop Synapses

Invest Ophthalmol Vis Sci 53(4):2007-19

Publication Date: April 18, 2012

Product Type: iCell GABANeurons,

Summary:

MyCell iPS Cells were used to generate optical vesicle-like structures that have the capacity to self-assemble into rudimentary neuroretinal structures that express markers indicative of chemical and electrical synapses.

Impact:

MyCell iPS Cells were differentiated into retinal cell types and structures that can be used for disease modeling and early investigational studies toward the application of iPS cells for future regenerative medicine applications.

January 2012

Whitemarsh RC, Strathman MJ, Chase LG, Stankewicz C, Tepp WH, Johnson EA, and Pellett S

Novel Application of Human Neurons Derived from Induced Pluripotent Stem Cells for Highly Sensitive Botulinum Neurotoxin Detection

Toxicol Sci 126(2):426-35

Publication Date: January 5, 2012

Product Type: iCell GABANeurons

Summary:

iCell Neurons were identified as a functionally relevant human model to detect and study Clostridium botulinum neurotoxin (BoNT). Compared with primary rat spinal cord cells, iCell Neurons showed equal or increased sensitivity, improved dose-response, and more complete SNARE protein cleavage in response to BoNT treatment.

Impact:

iCell Neurons are rapidly being adopted by academic researchers to study mechanisms of BoNT toxicity, as well as by BoNT manufacturers to detect and measure BoNT potency.

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

Mack AA, Kroboth S, Rajesh D, and Wang WB

Generation of Induced Pluripotent Stem Cells from CD34+ Cells across Blood Drawn from Multiple Donors with Non-integrating Episomal Vectors

PLoS One 6(11):e27956

Publication Date: November 22, 2011

Product Type: CDI Technology, iCell Products

Summary:

Demonstration of reprogramming from a single vial of blood or less using cells expressing the early lineage marker CD34 as well as from unpurified peripheral blood mononuclear cells.

Impact:

The methodology described demonstrates the creation of induced pluripotent stem cells from blood samples without the use of integrating reprogramming vectors, avoiding modifications of the donor genome while utilizing the least invasive sampling methodology.

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

Dias J, Gumenyuk M, Kang H, Vodyanik M, Yu J, Thomson JA, and Slukvin II

Generation of Red Blood Cells from Human Induced Pluripotent Stem Cells

Stem Cells Dev 20(9):1639-47

Publication Date: September 20, 2011

Product Type: CDI Technology, iCell Products

Summary:

Description of an approach for the efficient generation of RBCs from hiPSC/hESCs using an OP9 co-culture system to induce hematopoietic differentiation followed by selective expansion of erythroid cells in serum-free media with erythropoiesis-supporting cytokines.

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.