Selected CDI-related Publications

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iCell Cardiomyocytes

iCell Cardiomyocytes

References

Notes

Rao C, Prodromakis T, et al. (2013)
The Effect of Microgrooved Culture Substrates on Calcium Cycling of Cardiac Myocytes Derived from Human Induced Pluripotent Stem Cells.
Biomaterials 34(10):2399-411.

Publication date: Dec 20, 2013

Summary: Cellular alignment, sarcomeric organization, and Ca2+ cycling properties were altered when iCell Cardiomyocytes were cultured on a structured substrate.
Impact: This manuscript is an example of the value in combining advanced cell culture techniques with advanced cellular biology can create a more robust recapitulation of native cellular behavior.

Uesugi M, Ojima A, et al. (2013)
Low-density Plating Is Sufficient to Induce Cardiac Hypertrophy and Electrical Remodeling in Highly Purified iPS Cell-derived Cardiomyocytes.
J Pharmacol Toxicol Methods.69(2):177-88.

Publication date: Dec 1, 2013

Summary: Cardiac hypertrophy was induced in iCell Cardiomyocytes through low-density plating. The hypertrophic condition resulted in larger cardiomyocytes and altered gene and protein expression profiles.
Impact: This body of work demonstrates that iCell Cardiomyocytes can be induced to show relevant and appropriate pathological responses and provide utility as an in vitro model for understanding and treating cardiac disease.

Sirenko O, Cromwell EF, et al. (2013)
Assessment of Beating Parameters in Human Induced Pluripotent Stem Cells Enables Quantitative In Vitro Screening for Cardiotoxicity.
Toxicol Appl Pharmacol 273(3):500-07.

Publication date: Oct 1, 2013

Summary: High throughput protein-based assays were developed with iCell Cardiomyocytes as a system to induce and ameliorate hypertrophy.
Impact: This research demonstrates the practicality and utility of utilizing relevant native human biology in disease modeling and high throughput screens for drug discovery.

Carlson C, Koonce C, et al. (2013)
Phenotypic Screening with Human iPS Cell-derived Cardiomyocytes: HTS-compatible Assays for Interrogating Cardiac Hypertrophy.
J Biomol Screen 18(10):1203-11.

Publication date: Sep 26, 2013

Summary: High throughput protein-based assays were developed with iCell Cardiomyocytes as a system to induce and ameliorate hypertrophy.
Impact: This research demonstrates the practicality and utility of utilizing relevant native human biology in disease modeling and high throughput screens for drug discovery.

Guo L, Coyle L, et al. (2013)
Refining the Human iPSC-cardiomyocyte Arrhythmic Risk Assessment Model.
Toxicol Sci 136(2):581-94.

Publication date: Sep 19, 2013

Summary: iCell Cardiomyocytes were able to predict QT prolongation and arrhythmia with greater accuracy than current in vitro models when challenged with a set of 118 public and proprietary compounds.
Impact: This study demonstrates that iCell Cardiomyocytes provide improved proarrhythmia predictions on a higher throughput screening platform thus providing value-added data with fewer resources.

Cameron BJ, Gerry AB, et al. (2013)
Titin-derived HLA-A1-presented Peptide as a Cross-reactive Target for Engineered MAGE A3-directed T Cells
Sci Transl Med 5(197):197ra103.

Publication date: Aug 8, 2013

Summary: A T cell-based adoptive immunotherapy was developed and deemed to be free of off-target recognition or safety worries by extensive preclinical investigations. Administration to humans resulted in separate severe cardiotoxicity-related adverse event and fatality. Subsequent investigations showed cross-reactivity with cardiac Titin in a highly species-specific manner that was detectable in iCell Cardiomyocytes but not primary cultures of human cardiac cells maintained under the same conditions.
Impact: This manuscript demonstrates the need for culture systems that more fully recapitulate the native condition, even for highly specific immune-based drug discovery efforts.

Ivashchenko CY, Pipes GC, et al. (2013)
Human-Induced Pluriopotent Stem Cell-derived Cardiomyocytes Exhibit Temporal Changes in Phenotype
Am J Physiol Heart Circ Physiol 305(6):H913-22.

Publication date: Jul 5, 2013

Summary: In culture, iCell Cardiomyocytes progressively develop a more mature phenotype without signs of dedifferentiation. This phenotype is characterized by adult-like gene expression patterns, action potentials exhibiting ventricular atrial and nodal properties, coordinated calcium cycling and mechanical activity with pharmacological responses to pathologic (ET-1), physiologic (IGF-1) and autonomic (isoproterenol) stimuli similar to those characteristic of isolated adult cardiac myocytes.
Impact: This study demonstrates that iCell Cardiomyocytes recapitulate native tissue characteristics.

Fine M, Lu F, et al. (2013)
Human Induced Pluripotent Stem Cell-derived Cardiomyocytes for Studies of Cardiac Ion Transporters.
Am J Physiol Cell Physiol. 305(5):C481-91

Publication date: Jun 26, 2013

 

Summary: iCell Cardiomyocytes were analyzed for cardiac ion transporter function. Data demonstrate that iCell Cardiomyocytes exhibit human adult-like expression of major cardiac ion transporters, are amenable to long-term molecular manipulation of individual transporter and regulatory proteins, and can be used for analysis of transporter and regulatory protein turnover.
Impact: Data support the use of iCell Cardiomyocytes for a wide range of new cellular and molecular experimentation that was previously not possible to elucidate the molecular function and regulation of ion transporters.

Doherty K, Wappel R, et al. (2013)
Multiparameter In Vitro Toxicity Testing of Crizotinib, Sunitinib, Erlotinib, and Nilotinib in Human Cardiomyocytes.
Toxicol Appl Pharmacol 272(1):245-55.

Publication date: May 21, 2013

Summary: Tyrosine kinase inhibitors (TKi) have an established therapeutic value but also have associated cardiotoxicity that is not detected by standard pre-clinical models. iCell Cardiomyocytes and multiparametric analysis correctly predicted the cardiotoxic profile of four FDA-approved TKi molecules that showed unexpected toxicity in humans.
Impact: The data here demonstrate the value of utilizing functional human cardiac biology in pre-clinical testing to alleviate and avoid costly adverse events in clinical trials and the general population.

Harris K, Aylott M, et al. (2013)
Comparison of Electrophysiological Data from Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (hiPSC-CMs) to Functional Pre-clinical Safety Assays.
Toxicol Sci. 134(2):412-26

Publication date: May 20, 2013

Summary: Analysis of the cardiotoxic responses to known ion channel blockers and proprietary GSK compounds using iCell Cardiomyocytes and a multielectrode array (MEA) platform. iCell Cardiomyocytes demonstrate relevant pharmacology that correlates with existing pre-clinical assays.
Impact: This is the first study to demonstrate that in addition to showing relevant human physiology and pharmacology, iCell Cardiomyocytes’ responses to known cardiotoxic agents correlate to existing pre-clinical assays. Translation between novel iCell Cardiomyocytes assays and other pre-clinical assays is critical for drug discovery and safety studies to be considered in the regulatory environment.

Khan JM, Lyon AR, and Harding SE. (2013)
Case for Induced Pluripotent Stem cell-derived Cardiomyocytes in Pharmacological Screening
Pharmacol.169(2):304-17.

Publication date: Apr 26, 2013

Summary: This review assesses state-of-the art technology as of 2013; noting the advantages, potentials, and limitations of stem cell-derived cardiomyocytes in pharmacological screening.
Impact: The data and references within this review provide readers with peer-reviewed demonstrations of stem cell-derived cardiomyocyte utility. Many of the shortcomings and/or gaps in the technology are being (or have been) addressed by CDI.

Jehle J, Ficker E, et al. (2013)
Mechanisms of Zolpidem-induced Long QT Ayndrome: Acute Inhibition of Recombinant hERG K+ Channels and Action Potential Prolongation in Human Cardiomyocytes Derived from Induced Pluripotent Stem Cells.
British J Pharm 168:1215-29.

Publication date: Feb 21, 2013

Summary: iCell Cardiomyocytes exhibited prolongation of cardiac action potential duration in response to zolpidem, a short-acting hypnotic drug prescribed to treat insomnia that has been clinically associated with acquired long QT syndrome (LQTS) and torsade de pointes (TdP).
Impact: iCell Cardiomyocytes treated with a known toxic drug compound showed biochemical responses that mimic toxic responses observed in the clinic, demonstrating that iCell Cardiomyocytes are a relevant in vitro model to predict human cardiotoxicity.

Schweikart K, Guo L, et al. (2012)
The Effects of Jaspamide on Human Cardiomyocyte Function and Cardiac Ion Channel Activity.
Toxicol in Vitro 27:745-51.

Publication date: Dec 20, 2012

Summary: iCell Cardiomyocytes were used to demonstrate that the acute clinical toxicity of jaspamide, an anti-neoplastic agent, is due to drug-induced cardiotoxicity.
Impact: iCell Cardiomyocytes were used to elucidate mechanisms of action of an anti-cancer drug associated with clinical toxicity.

Wei H, Zhang G, et al. (2012)
Suppresses Outward Rectifier Potassium Currents in Human Pluripotent Stem Cell-derived Cardiomyocytes.
Plos One 7(11):e50641.

Publication date: Nov 30, 2012

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.

Puppala D, Collis LP, et al. (2013)
Comparative Gene Expression Profiling in Human Induced Pluripotent Stem Cell Derived Cardiocytes and Human and Cynomolgus Heart
Tissue. Toxicol Sci 131:292-301.

Publication date: Sep 14, 2012

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, Crittenden C, et al. (2013)
Multiparameter In Vitro Assessment of Compound Effects on Cardiomyocyte Physiology Using iPS Cells.
J Biomol Screening 18:39-53

Publication date: Sep 12, 2012

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.

Cerignoli R, Charlot D, et al. (2012)
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: Aug 25, 2012

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, et al. (2012)
Development of High Content Imaging Methods for Cell Death Detection in Human Pluripotent Stem Cell-derived Cardiomyocytes.
J of Cardiovasc Trans Res 5:593- 604.

Publication date: Aug 16, 2012

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.

Rana P, Anson BD, et al. (2012)
Characterization of Human-induced Pluripotent Stem Cell-derived Cardiomyocytes: Bioenergetics and Utilization in Safety Screening.
Toxicol Sci 130:117-31.

Publication date: Jun 27, 2012

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, et al. (2012)
Whole-exome Sequencing and an iPSC-derived Cardiomyocyte Model Provides a Powerful Platform for Gene Discovery in Left Ventricular Hypertrophy.
Frontiers in Genetics 3:92.

Publication date: Jun 02, 2012

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 patient 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.

Lee P, Kloss M, et al. (2012)
Simultaneous Voltage and Calcium Mapping of Genetically Purified Human Induced Pluripotent Stem Cell-derived Cardiac Myocyte Monolayers.
Circ Res 110:1556-63.

Publication date: May 8, 2012

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.

Reynolds JG, Geretti E, et al. (2012)
HER2-targeted Liposomal Doxorubicin Displays Enhanced Anti-tumorigenic Effects without Associated Cardiotoxicity.
Toxicol Appl Pharmacol 262:1-10.

Publication date: Apr 21, 2012

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.

Babiarz JE, Ravon M, et al. (2012)
Determination of the Human Cardiomyocyte mRNA and miRNA Differentiation Network by Fine-scale Profiling.
Stem Cells Dev 21:1956-65.

Publication date: Jan 4, 2012

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.

Jonsson MKB, Wang QD, et al. (2011)
Impedance- based Detection of Beating Rhythm and Proarrhythmic Effects of Compounds on Stem Cell- derived Cardiomyocytes.
Assay and Drug Dev Tech 9:1-11.

Publication date: Nov 15, 2011

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

Ma J, Guo L, et al. (2011)
High Purity Human-induced Pluripotent Stem Cell-derived Cardiomyocytes: Electrophysiological Properties of Action Potentials and Ionic Currents.
Am J Physiol Heart Circ Physiol 301:H2006-H2017.

Publication date: Sep 2, 2011

 

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.

Cohen JD, Babiarz JE, et al. (2011)
Use of Human Stem Cell-derived Cardiomyocytes to Examine Sunitinib Mediated Cardiotoxicity and Electrophysiological Alterations.
Toxicol Appl Pharmacol 257:74-83.

Publication date: Aug 27, 2011

Summary: Elucidation of the molecular mechanisms of sunitinib-induced cardiotoxicity using iCell Cardiomyocytes revealed that contrary to previous data using rodent models, 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.

Guo L, Abrams RM, et al. (2011)
Estimating the Risk of Drug-induced Proarrhythmia Using Human Induced Pluripotent Stem Cell-derived Cardiomyocytes.
Toxicol Sci 123:281-289.

Publication date: Jun 20, 2011

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, et al. (2011)
The Electrophysiological Effects of Cardiac Glycosides in Human iPSC-derived Cardiomyocytes and in Guinea Pig Isolated Hearts.
Cell Physiol Biochem 27:453-462.

Publication date: Jun 15, 2011

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

iCell Neurons

iCell Neurons

References

Notes

Alhebshi AH, Odawara A1, Gotoh M, Suzuki I (2014)
Thymoquinone protects cultured hippocampal and human induced pluripotent stem cells-derived neurons against α-synuclein-induced synapse damage.

Neurosci Lett. 570:126-31

Publication date: Jun 6, 2014

Summary: Synapse density, synaptic vesicle recycling and electrical activity in iCell Neurons before and after treatment with α-synuclein and thymoquinone (TQ) was assessed. iCell Neurons exhibited toxicity to α-synuclein (α-SN) which was reduce upon treatment with TQ.
Impact: α-SN-induced synaptic damage is involved in Parkinson’s disease and dementia with Lewy bodies. Using iCell Neurons, thymoquinone (TQ) showed neuroprotection against α-SN-induced synaptic toxicity. iCell Neurons are a relevant and reliable cell type to discover potential therapeutics for neurodegenerative diseases.

 

Dage JL, Colvin EM, et al. (2014)
Pharmacological characterisation of ligand- and voltage-gated ion channels expressed in human iPSC-derived forebrain neurons.
Psychopharmacology (Berl). 231(6):1105-24.

Publication date: Jan 7, 2014

Summary: Gene expression analysis and functional characterization (using FLIPR) of the ion channels (Ca and Na) and receptors (AMPA, NMDA, and GAB) involved in synaptic physiology were performed on iCell Neurons.
Impact: This study demonstrated that iCell Neurons show higher correlation with the prefrontal cortex and they exhibit functional ionotropic glutamate receptors (AMPA and NMDA) and GABAA receptors. iCell Neurons are a good cellular model of a forebrain human neuron population that can be used both as a control or host of genetic mutations in genetic neurological disease studies (ASD).

 

Odawara A, Saito Y, et al. (2014)
Long-term electrophysiological activity and pharmacological response of a human induced pluripotent stem cell-derived neuron and astrocyte co-culture.
BBRC 443:1176-1181.

Publication date: Jan 7, 2014

Summary: iCell Neurons were co-cultured with rat primary astrocytes to study the effects of a co-culture environment on the longevity, spontaneous firing activity and drug response on the neurons as measured by MEA.
Impact: iCell Neurons were maintained in culture with the rat astrocytes for an extend period of time (>120 days) and they were able to maintain long-term spontaneous firing that can be modulated with synapse antagonists drugs and detect synchronicity.

Whitemarsh RC, Tepp WH, et al. (2013)
Characterization of Botulinum Neurotoxin A Subtypes 1 Through 5 by Investigation of Activities in Mice, in Neuronal Cell Cultures, and In Vitro.
Infect Immun 81: 3894-3902.

Publication date: Aug 5, 2013

Summary: iCell Neurons, along with other commonly used in vitro and in vivo models, were used to characterize the various subtypes of BoNT/A. The results showed distinct in vitro and in vivo toxicological properties between the mouse bioassay (MBA) and in vitro human cell models, thus questioning the predictivity of the MBA.
Impact: This study supports the need to consider not only the mode of the testing (in vivo versus in vitro) but also the species of the model when designing potency assays for current and future pharmaceutical BoNT preparations. iCell Neurons area relevant human model to detect BoNT.

Grose C, Xiaoli Y, et al. (2013)
Aberrant Virion Assembly and Limited gC Production in Varicella Zoster Virus Infected Neurons.
J Virol.87(17):9643-8

Publication date: Jun 26, 2013

Summary: An iCell Neuron in vitro model of varicella zoster virus (VZV) infection developed by Yu, et al (2013) was used in a subsequent study to determine whether diminished production of virion components and/or final assembly of complete virions play a role in limiting productive virus infection.
Impact: Primary VZV infection typically produces varicella (chickenpox), after which the virus becomes latent. Reactivation of the virus produces zoster (shingles), which is a more serious disease characterized by chronic pain and other neurological problems. iCell Neurons are used to model VZV infection and better define the molecular underpinnings of the virus-host relationship.

Gill J, Chatzidaki A, et al. (2013)
Contrasting Properties of α7-Selective Orthosteric and Allosteric Agonists Examined on Native Nicotinic Acetylcholine Receptors.
PLoS ONE 8:e55047.

Publication date: Jan 29, 2013

Summary: iCell Neurons were used to evaluate the potential use of three pharmacologically distinct α7-selective nicotinic ligands (an orthosteric agonist, a positive allosteric modulator, and a nondesensitizing allosteric agonist) for the characterization of native nAChRs.
Impact: iCell Neurons were shown to be a relevant human model to identify and characterize ligands that are specific for particular receptor subtypes implicated in neurological and psychiatric disorders. The identification of such reagents will accelerate academic research and pharmaceutical drug discovery.

Yu X, Sietz S, et al. (2013)
Varicella Zoster Virus Infection of Highly Pure Terminally Differentiated Human Neurons.
J Neurovirol 19:75-81.

Publication date: Dec 12, 2012

Summary: iCell Neurons were used to develop a novel in vitro model of varicella zoster virus (VZV) infection. Infection of iCell Neurons with VZV yields a non- productive infection with detectable expression of immediate-early, early, and late viral genes, but no evidence of apoptosis, which together will enable molecular analysis of VZV-neuron interactions and mechanisms of VZV reactivation.
Impact: iCell Neurons provided a biologically relevant human cell model to study mechanisms of VZV infection, which was previously not possible using primary neuronal cells due to limitations in cell functionality and purity.

Xu X, Lei Y, et al. (2013)
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 10:213-227.

Publication date: Dec 7, 2012

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.

Haythornthwaite A, Stoelzle A, et al. (2012)
Characterizing Human Ion Channels in Induced Pluripotent Stem Cell-derived Neurons.
J Biomol Screen 17:1264-1272.

Publication date: Aug 24, 2012

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.

Chai X, Dage JL, et al. (2012)
Constitutive Secretion of Tau Protein by an Unconventional Mechanism.
Neurobiol Dis 48:356-366

Publication date: Jun 2, 2012

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.

Whitemarsh RC, Strathman MJ, et al. (2012)
Novel Application of Human Neurons Derived from Induced Pluripotent Stem Cells for Highly Sensitive Botulinum Neurotoxin Detection.
Toxicol Sci 126:426-35.

Publication date: Jan 5, 2012

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.

iCell Hepatocytes

iCell Hepatocytes

References

Notes

Sirenko O, Hesley J, Rusyn I, and Cromwell EF. (2013)
High-content Assays for Hepatotoxicity Using Induced Pluripotent Stem Cell-derived Cells.
Assay Drug Dev Technol. 12(1):43-54.

Publication date: Nov 14, 2013

Summary: iCell Hepatocytes were employed in the screening of a panel of 208 known hepatotoxic and 30 safe compounds by high content analysis for multiple toxic endpoint readouts.
Impact: The predictive power of the iCell Hepatocytes in assessing compound hepatotoxicity suggests their utility as in vitro assay models for toxicity screening and understanding potential hepatotoxic effects early in the drug development process.

iCell Endothelial Cells

iCell Endothelial Cells

References

Notes

Gui, L. and Niklason, L.E. (2014)
Vascular Tissue Engineering: Building Perfusable Vasculature for Implantation
Curr Opin Chem Eng 3:68-74.

Publication date: Feb 7, 2014

Summary: A review article describing the state of the art for vascular biology in generating perfusable tissues for therapeutic applications. The potential for iPSC-derived endothelial cells in such applications is reported.
Impact: iCell Endothelial Cells are currently commercially available as iCell Endothelial Cells (Cellular Dynamics International). As such, human iPSCs offer the advantages of providing a possibly unlimited number of autologous ECs to vascularize tissue engineered constructs for implantation.

MyCell Products

MyCell Products

References

Notes

Phillips MJ, Wallace KA, et al. (2012)
Blood-derived Human iPS Cells Generate Optic Vesicle-like Structures with the Capacity to Form Retinal Laminae and Develop Synapses.
Inv Opthamology and Visual Sci 53:2007-2019.

Publication date: Mar 14, 2012

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.

Cellular Dynamics Technology

CDI Research

References

Notes

Mack AA, Kroboth S, et al. (2011)
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

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.

Ma J, Guo L, et al. (2011)
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 

Summary: Performance of detailed electrophysiological characterization of highly pure hiPSC-derived cardiomyocytes. Action potentials (APs) were recorded from spontaneously beating cardiomyocytes using a perforated patch method and had atrial-, nodal-, and ventricular-like properties.

Rajesh D, Dickerson S, et al (2011) Human Lymphoblastoid B Cell Lines Reprogrammed to EBV-free Induced Pluripotent Stem Cells
Blood 118(7):1797-1800

Summary: Generation of iPSCs from two LCLs via a feeder-free episomal method using a cocktail of transcription factors and small molecules. LCL-derived iPSCs exhibited normal karyotype, expressed pluripotency markers, lost oriP/EBNA-1 episomal vectors, generated teratomas, retained donor identity and differentiatedin vitro into hematopoietic, cardiac, neural, and hepatocyte-like lineages.

Anson BD, Kolaja KL, and Kamp TJ (2011)
Opportunities for Use of Human iPS Cells in Predictive Toxicology
Clin Pharmacol Ther 89(5):754-758

Summary: Description of the properties of human induced pluripotent stem (iPS) cells that make them a promising source for toxicity assessment, highlight the progress to date, and point out the important roadblocks that remain.

Stem Cell Publications

References

Notes

Phillips MJ, Wallace KA, et al (2012)
Blood-derived Human iPS Cells Generate Optic Vesicle-like Structures with the Capacity to Form Retinal Laminae and Develop Synapses
Ophthalmol Vis Sci 53(4):2007-2019

Summary: Demonstration that human blood-derived iPSCs can generate retinal cell types and that cultured TiPSC-OVs have the capacity to self-assemble into rudimentary neuroretinal structures and express markers indicative of chemical and electrical synapses.

Meyer JS, Howden SE, et al.(2011)
Optic Vesicle Structures Derived from Human Pluripotent Stem Cells Facilitate a Customized Approach to Retinal Disease Treatment
Stem Cells 29:1206–1218

Summary: Demonstration that three-dimensional populations of retinal progenitor cells (RPCs) can be isolated from early forebrain populations in both human embryonic stem cell and hiPSC cultures, providing a valuable tool for developmental, functional, and translational studies. Using the established protocol, a transient population of optic vesicle (OV)-like structures that arose during a time period appropriate for normal human retinogenesis were identified.

Dias J, Gumenyuk M, et al. (2011)
Generation of Red Blood Cells from Human Induced Pluripotent Stem Cells
Stem Cells Dev 20(9):1639-47

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.

Slukvin II and Vodyanik M (2011)
Endothelial Origin of Mesenchymal Stem Cells
Cell Cycle 10(9):1370-3

Summary: Demonstrating that mesodermal MSCs arise from APLNR+ precursors with angiogenic potential, mesenchymoangioblasts.

Chen G, Gulbranson DR, et al (2011)
Chemically Defined Conditions for Human iPS Cell Derivation and Culture

Nat Methods 8(5):424–429

Summary: Use of new medium (E8) and vitronectin-coated surfaces to demonstrate improved derivation efficiencies of vector-free human iPS cells with an episomal approach.

Howden SE, Gore A, et al. (2011)
Genetic Correction and Analysis of Induced Pluripotent Stem Cells from a Patient with Gyrate Atrophy

Proc Natl Acad Sci USA 108(16):6537-6542

Summary: Isolation of iPS cells free of transgene sequences from a patient with gyrate atrophy caused by a point mutation in the gene encoding ornithine-δ-aminotransferase (OAT) and use of homologous recombination to correct the genetic defect.

Yu J, Chau FK, et al (2011)
Efficient Feeder-Free Episomal Reprogramming with Small Molecules

PLoS ONE 6(3):e17557

Summary: Establishment of a feeder-free reprogramming condition using chemically defined medium with bFGF and N2B27 supplements and chemically defined human ESC medium mTeSR1 for the derivation of footprint-free human iPSCs.

Hu K, Yu J, et al. (2011)
Efficient Generation of Transgene-free Induced Pluripotent Stem Cells from Normal and Neoplastic Bone Marrow and Cord Blood Mononuclear Cells
Blood 117:14e109-e119

Summary: Demonstrated that iPSCs free of transgene and vector sequences could be efficiently generated from human bone marrow (BM) and cord blood (CB) mononuclear cells using non-integrating episomal vectors.

Brown ME, Rondon E, et al (2010)
Derivation of Induced Pluripotent Stem Cells from Human Peripheral Blood T Lymphocytes

PLoS ONE 5(6): e11373

Summary: Generation of T lymphocyte-derived iPSCs from small, clinically advantageous volumes of non-mobilized peripheral blood. These T-cell derived iPSCs retain a normal karyotype and genetic identity to the donor.

Yu J and Thomson JA (2009)
Induced Pluripotent Stem Cell Derivation
Essentials of Stem Cell Biology, 2nd edition, Elsevier Academic Press

Summary: Description of basic biology/mechanisms, early development, ectoderm, mesoderm, endoderm, methods to application of stem cells to specific human diseases, regulation and ethics, and patient perspectives, and more in the field of stem cells.

Yu J, Hu K, et al (2009)
Human Induced Pluripotent Stem Cells Free of Vector and Transgene Sequences

Science 324(5928):797-801

Summary: Derivation of human iPS cells with the use of nonintegrating episomal vectors.

Ebert AD, Yu J, et al (2008)
Induced Pluripotent Stem Cells from a Spinal Muscular Atrophy Patient

Nature 457(7227):277-80

Summary: Generation of induced pluripotent stem cells from skin fibroblast samples taken from a child with spinal muscular atrophy.

Yu J and Thomson JA (2008)
Pluripotent Stem Cell Lines
Genes Dev 22(15):1987-97

Summary: Review of the family of pluripotent cell lines derived from early embryos and from germ cells, comparing them with more recently described induced pluripotent stem cells.

Yu J, Vodyanik MA, et al (2007)
Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells

Science 318(5858):1917-20

Summary: Showing that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem cells.

Yu J, Vodyanik MA, et al (2005)
Human Embryonic Stem Cells Reprogram Myeloid Precursors Following Cell-Cell Fusion
Stem Cells 24(1):168-76

Summary: Reprogramming of the nuclei of hESC-derived myeloid precursors following cell-cell fusion.