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March 2015

Berger DR, Ware BR, Davidson MD, Allsup SR, and Khetani SR

Enhancing the Functional Maturity of iPSC-derived Human Hepatocytes via Controlled Presentation of Cell-Cell Interactions In Vitro

Hepatology 61(4):1370-81

Publication Date: March 25, 2015

Product Type: iCell Hepatocytes

Summary:

iCell Hepatocytes were cultured in micropatterned islands and co-cultured with mouse fibroblasts to achieve more functionally mature phenotypes including CYP450s (basal and induced), maturity markers (gene expression), and toxin sensitivity.

Impact:

This research highlights the application of iCell Hepatocytes in more complex (organotypic) culture environments and suggests that appropriate culture conditions and signaling mechanisms lead to more mature iCell Hepatocytes.

February 2015

Ware BR, Berger DR, Khetani SR

Prediction of Drug-Induced Liver Injury in Micropatterned Co-cultures Containing iPSC-Derived Human Hepatocytes

Tox Sci 145(2):252-62

Publication Date: February 24, 2015

Product Type: iCell Hepatocytes

Summary:

iCell Hepatocytes were cultured in micropatterned islands and co-cultured with mouse fibroblasts to achieve more functionally mature phenotypes including CYP450s (basal and induced), maturity markers (gene expression), and toxin sensitivity.

Impact:

This research highlights the application of iCell Hepatocytes in more complex (organotypic) culture environments and suggests that appropriate culture conditions and signaling mechanisms lead to more mature iCell Hepatocytes.

Ng S, Schwartz RE, March S, Galstian A, Gural N, Shan J, Prabhu M, Mota MM, Bhatia SN

Human iPSC-derived Hepatocyte-like Cells Support Plasmodium Liver-stage Infection In Vitro

Stem Cell Reports 4(3):348-359

Publication Date: February 7, 2015

Product Type: iCell Hepatocytes

Summary:

iCell Hepatocytes were employed as a model for malaria parasite infection. Cells were infected with Plasmodium falciparum and and Plasmodium vivax species.

Impact:

The study demonstrates the application of iCell Hepatocytes for infectious disease research enabling malaria research for parasitic life cycle modeling as well as drug discovery efforts.

November 2014

Caralt M, Uzarski JS, Iacob S, Obergfell KP, Berg N, Bijonowski BM, Kiefer KM, Ward HH, Wandinger-Ness A, Miller WM, Zhang ZJ, Abecassis MM, and Wertheim JA

Optimization and Critical Evaluation of Decellularization Strategies to Develop Renal Extracellular Matrix Scaffolds As Biological Templates for Organ Engineering and Transplantation

Am J Transplant 15(1):64-75

Publication Date: November 17, 2014

Product Type: iCell Endothelial Cells

Summary:

iCell Endothelial Cells were used to reform the vasculature in a decellularized rat kidney. The cells were fluorescently tagged to enable visualization of the vascular network.

Impact:

This research is a milestone in the advancement of generating transplantable tissue, either autologous or allogeneic.

Mann DA

Human Induced Pluripotent Stem Cell-derived Hepatocytes for Toxicology Testing

Expert Opin Drug Metab Toxicol 11(1):1-5

Publication Date: November 11, 2014

Product Type: iCell Hepatocytes

Summary:

This editorial describes the current utility of iPSC-derived hepatocytes in toxicological tests, suggesting the shortcomings of stem cell hepatocytes can be overcome by application in organotypic culture models to generate more predictive in vitro assays.

Impact:

iCell Hepatocytes are compatible with and being employed in organotypic culture models. The combination of stem cell-derived hepatocytes and organotypic systems will synergize to generate highly predictive in vitro models.

October 2014

Drawnel FM, Boccardo S, Prummer M, Delobel F, Graff A, Weber M, Gérard R, Badi L, Kam-Thong T, Bu L, Jiang X, Hoflack JC, Kiialainen A, Jeworutzki E, Aoyama N, Carlson C, Burcin M, Gromo G, Boehringer M, Stahlberg H, Hall BJ, Magnone MC, Kolaja K, Chien KR, Bailly J, and Iacone R

Disease Modeling and Phenotypic Drug Screening for Diabetic Cardiomyopathy Using Human Induced Pluripotent Stem Cells

Cell Rep 9(3):810-820

Publication Date: October 30, 2014

Product Type: iCell Cardiomyocytes, MyCell Cardiomyocytes

Summary:

Researchers created in vitro models for environmental and genetically-driven diabetic cardiomyopathy. iCell Cardiomyocytes were induced to the cardiomyopathic state through incubation with a diabetic medium while diabetic donor-specific, iPSC-derived MyCell Cardiomyocytes showed the cardiomyopathy phenotype under baseline conditions. A small molecule screen identified molecules that reverted the cardiomyopathy in accordance with the clinical progression of the disease.

Impact:

This research validates using human iPSC-derived technology in phenotypic drug discovery. It demonstrates the recapitulation of cardiomyopathy through environmental and genetic mechanisms and establishes the utility of phenotypic screens to find molecules and pathways that may provide a therapeutic option.

Scherf JM, Hu XS, Tepp WH, Ichtchenko K, Johnson EA, Pellett S

Analysis of Gene Expression in Induced Pluripotent Stem Cell-Derived Human Neurons Exposed to Botulinum Neurotoxin A Subtype 1 and a Type A Atoxic Derivative

PLoS One 9(10):e111238

Publication Date: October 22, 2014

Product Type: iCell Neurons

Summary:

iCell Neurons were exposed to BoNT and an inactive BoNT derivative to analyze the BoNTs effects on gene expression. Significant transcriptional changes were observed at 14 days post intoxication, specifically in genes related to Ca2+ channel signaling and neurite sprouting.

Impact:

An inactive BoNT derivative has been proposed as a general delivery vehicle to target compounds to neurons. iCell Neurons provided a human model to assess the effects of BoNT and variants to investigate this delivery method.

September 2014

Aggarwal P, Turner A, Matter A, Kattman SJ, Stoddard A, Lorier R, Swanson BJ, Arnett DK, and Broeckel U

RNA Expression Profiling of Human iPSC-derived Cardiomyocytes in a Cardiac Hypertrophy Model

PLoS One 9(9):e108051

Publication Date: September 25, 2014

Product Type: iCell Cardiomyocytes

Summary:

Cardiac hypertrophy is characterized by phenotypic, molecular, and genomic changes. This work induced hypertrophy in iCell Cardiomyocytes, demonstrated overlap in transcriptional changes between induced iCell Cardiomyocytes and biopsied cardiac tissue from donor’s with left ventricular hypertrophy, and isolated a unique micro-RNA / mRNA pairing that provided further insight to a complex disease etiology.

Impact:

Most diseases have complex origins and presentations. This work exemplifies the power of iPSC-derived models to recapitulate disease states, elucidate novel molecular entities associated with disease states, and provide insight as to causes and potential therapeutic avenues.

Hayakawa T, Kunihiro T, Ando T, Kobayashi S, Matsui E, Yada H, Kanda Y, Kurokawa J, and Furukawa T

Image-based Evaluation of Contraction–Relaxation Kinetics of Human-induced Pluripotent Stem Cell-derived Cardiomyocytes: Correlation and Complementarity with Extracellular Electrophysiology

J Mol Cell Cardiol 77:178-91

Publication Date: September 23, 2014

Product Type: iCell Cardiomyocytes

Summary:

Researchers used label-free imaging for examining contractility. Cross-platform comparison with electrophysiology, intracellular Ca2+, and traction-force microscopy demonstrated appropriate readout. Functional validation with Na+ channel block, hERG channel block, and beta adrenergic stimulation showed utility for examining cardiomyocyte contraction rate, force, and relaxation.

Impact:

Label-free imaging enables investigators to apply quantitative metrics to iCell Cardiomyocytes’ contractility endpoints in a higher throughput fashion.

Scott CW, Zhang X, Abi-Gerges N, Lamore SD, Abassi YA, and Peters MF

An Impedance-based Cellular Assay Using Human iPSC-derived Cardiomyocytes to Quantify Modulators of Cardiac Contractility

Toxicol Sci 142(2):331-8

Publication Date: September 18, 2014

Product Type: iCell Cardiomyocytes

Summary:

iCell Cardiomyocytes and impedance measurements were shown to be a suitable system for assessing drug-induced effects on contractility. This system was more predictive than rat cardiomyocytes, had assay parameters similar to the gold standard system, and provided higher throughput.

Impact:

This research demonstrates the utility of iCell Cardiomyocytes as a screening model for assessing contractility changes.

Gibson JK, Yue Y, Bronson J, Palmer C, and Numann R

Human Stem Cell-derived Cardiomyocytes Detect Drug-mediated Changes in Action Potentials and Ion Currents

J Pharmacol Toxicol Methods 70(3):255-67

Publication Date: September 16, 2014

Product Type: iCell Cardiomyocytes

Summary:

Researchers recorded action potentials from isolated iCell Cardiomyocytes before and after drug exposure. The recorded responses were stable, sensitive, and robust, demonstrating the appropriate human cardiac electrophysiology and pharmacology.

Impact:

Proarrhythmia prediction can be done at the phenotypic and mechanistic level. This paper complements the growing literature on phenotypic prediction with iCell Cardiomyocytes by demonstrating valid underlying mechanistic processes and pharmacology.

Traister A, Li M, Aafaqi S, Lu M, Arab S, Radisic M, Gross G, Guido F, Sherret J, Verma S, Slorach C, Mertens L, Hui W, Roy A, Delgado-Olguín P, Hannigan G, Maynes JT, and Coles JG

Integrin-linked Kinase Mediates Force Transduction in Cardiomyocytes by Modulating SERCA2a/PLN Function

Nat Commun 5:4533

Publication Date: September 11, 2014

Product Type: iCell Cardiomyocytes

Summary:

Integrin-linked kinase (ILK) associates with protein scaffolding involved in mechanotransduction and contractility. iCell Cardiomyocytes were used to verify ILK as a potential therapeutic target; its modulation altered expression levels and function of other proteins in the scaffold, intracellular Ca2+ signaling, and contractility.

Impact:

This research demonstrates the utility of iCell Cardiomyocytes as a model system for target identification, verification, and screening. A target was identified, its value as a therapeutic target confirmed through over-expression and knockdown, and the functional impact assessed through phenotypic assays.

Belair DG, Whisler JA, Valdez J, Velazquez J, Molenda JA, Vickerman V, Lewis R, Daigh C, Hansen TD, Mann DA, Thomson JA, Griffith LG, Kamm RD, Schwartz MP, and Murphy WL

Human Vascular Tissue Models Formed from Human Induced Pluripotent Stem Cell Derived Endothelial Cells

Stem Cell Rev [Epub ahead of print]

Publication Date: September 5, 2014

Product Type: iCell Endothelial Cells

Summary:

iCell Endothelial Cells were cultured within several bioengineered platforms mimicking the in vivo microenvironment and formed vascular architecture to enable tissue engineering and discovery applications. Assays for measuring migration, invasion, and vascular sprouting in response to cytokines and inhibitors are also reported along with basic characterization data.

Impact:

This is the first iCell Endothelial Cells publication to illustrate multiple applications in bioengineering, vascular network formation, and angiogenesis for regenerative medicine, tissue engineering, toxicity, and discovery applications.

June 2014

Alhebshi AH, Odawara A, Gotoh M, and Suzuki I

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: June 6, 2014

Product Type: iCell Neurons

Summary:

Synapse density, synaptic vesicle recycling and electrical activity were assessed in iCell Neurons before and after treatment with α-synuclein and thymoquinone (TQ). iCell Neurons exhibited toxicity to α-synuclein, which was reduced upon treatment with TQ.

Impact:

Neuroprotection against synapse damage associated with Parkinson’s disease was demonstrated in iCell Neurons, providing evidence that these cells are a relevant system to discover potential therapeutics for neurodegenerative diseases.

April 2014

Nakamura Y, Matsuo J, Miyamoto N, Ojima A, Ando K, Kanda Y, Sawada K, Sugiyama A, and Sekino Y

Assessment of Testing Methods for Drug-induced Repolarization Delay and Arrhythmias in an iPS Cell–derived Cardiomyocyte Sheet: Multi-site Validation Study

J Pharmacol Sci 124(4):494-501

Publication Date: April 2, 2014

Product Type: iCell Cardiomyocytes

Summary:

The experimental robustness of iCell Cardiomyocytes was tested across three independent laboratories. hERG channel (IKr) block was assessed via MEA-measured field potential duration prolongation in each laboratory and found to be equivalent.

Impact:

These data demonstrate that iCell Cardiomyocytes utilized in standardized protocols provide inter-facility robustness and repeatability.

February 2014

Gui L and Niklason LE

Vascular Tissue Engineering: Building Perfusable Vasculature for Implantation

Curr Opin Chem Eng 3:68-74

Publication Date: February 7, 2014

Product Type: iCell Endothelial Cells

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 (ECs) 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.

January 2014

Dage JL, Colvin EM, Fouillet A, Langron E, Roell WC, Li J, Mathur SX, Mogg AJ, Schmitt MG, Felder CC, Merchant KM, Isaac J, Broad LM, Sher E, and Ursu D

Pharmacological Characterisation of Ligand- and Voltage-gated Ion Channels Expressed in Human iPSC-derived Forebrain Neurons

Psychopharmacology (Berl) 231(6):1105-24

Publication Date: January 7, 2014

Product Type: iCell Neurons

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, Saitoh Y, Alhebshi AH, Gotoh M, and Suzuki I

Long-term Electrophysiological Activity and Pharmacological Response of a Human Induced Pluripotent Stem Cell-derived Neuron and Astrocyte Co-culture

Biochem Biophys Res Commun 443(4):1176-81

Publication Date: January 7, 2014

Product Type: iCell Neurons

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.

December 2013

Rao C, Prodromakis T, Kolker L, Chaudhry UA, Trantidou T, Sridhar A, Weekes C, Camelliti P, Harding SE, Darzi A, Yacoub MH, Athanasiou T, and Terracciano CM

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: December 20, 2013

Product Type: iCell Cardiomyocytes

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, Taniguchi T, Miyamoto N, and Sawada K

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: December 1, 2013

Product Type: iCell Cardiomyocytes

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.

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