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May 2015

Komatsu M, Wheeler HE, Chung S, Low SK, Wing C, Delaney SM, Gorsic LK, Takahashi A, Kubo M, Kroetz DL, Zhang W, Nakamura Y, Dolan ME

Pharmacoethnicity in Paclitaxel-Induced Sensory Peripheral Neuropathy

Clin Cancer Res [Epub ahead of print]

Publication Date: May 26, 2015

Product Type: iCell Neurons

Summary:

iCell Neurons in combination with clinical GWAS studies for chemotherapy-induced peripheral neuropathies (CIPN) were used to identify the most promising genetic variants and genes associated with CIPN underlying ethnic specificity. iCell Neurons were used to validate gene function through the use of gene knockdown by siRNA transfection and neurite outgrowth assessment.

Impact:

iCell Neurons offer a relevant in vitro cell model to assist with the elucidation of variants specific to the Asian population that may be helpful in developing personalized cancer treatments.

April 2015

Pellett S, Tepp WH, Scherf JM, Pier, CL and Johnson EA

Activity of Botulinum Neurotoxin Type D (Strain 1873) in Human Neurons

Toxicon. 101: 63 - 9

Publication Date: April 30, 2015

Product Type: iCell Neurons

Summary:

iCell Neurons were used to examine BoNT/D activity, a lesser known BoNT derivative, in human cells. The results showed that BoNT/D can enter and cleave VAMP 2 but at a significantly lower efficiency and shorter duration of action than BoNT/A1, the common serotype used in the cosmetic industry and to a lesser degree as a therapeutic.

Impact:

This study supports the need to explore other serotypes, besides the more well-known types, that could be considered a potential bioterrorism attack and for potential use as a novel therapeutic or drug delivery method. iCell Neurons are a relevant human model to detect BoNT and further characterize its properties.

Chatzidaki A, Fouillet A, Li J, Dage J, Millar NS, Sher E, Ursu D

Pharmacological Characterisation of Nicotinic Acetylcholine Receptors Expressed in Human iPSC-Derived Neurons

PLoS One 10(4):e0125116

Publication Date: April 23, 2015

Product Type: iCell Neurons

Summary:

iCell Neurons were used to examine the expression and functional properties of nicotinic acetylcholine receptors (nAChRs). Gene expression analysis indicated the presence of transcripts encoding several nAChR subunits, α3-α7, β1, β2, and β4 subunits. In addition, similarly high transcript levels were detected for the truncated dupα7 subunit transcript, encoded by the partially duplicated gene CHRFAM7A, which has been associated with psychiatric disorders such as schizophrenia.

Impact:

Neuronal nAChRs have been implicated in a variety of neurological and psychiatric disorders, including Alzheimer’s disease, schizophrenia, depression and ADHD, thus drawing considerable interest, from both academia and pharma, in developing novel cellular assays. These cells therefore represent a great tool to advance the understanding of the properties of native human nAChRs.

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.

Diouf B, Crews KR, Lew G, Pei D, Cheng C, Bao J, Zheng JJ, Yang W, Fan Y, Wheeler HE, Wing C, Delaney SM, Komatsu M, Paugh SW, McCorkle JR, Lu X, Winick NJ, Carroll WL, Loh ML, Hunger SP, Devidas M, Pui CH, Dolan ME, Relling MV, Evans WE

Association of an Inherited Genetic Variant with Vincristine-related Peripheral Neuropathy in Children with Acute Lymphoblastic Leukemia

JAMA 313(8):815-23

Publication Date: February 24, 2015

Product Type: iCell Neurons

Summary:

 iCell Neurons were used to assess chemotherapeutic (vincristine)-induced toxicity and the relationship between CEP72 expression and the degree of patient sensitivity to vincristine. These data corroborate their clinical finding that an inherited polymorphism in CEP72 is associated with an increased risk and severity of vincristine-related peripheral neuropathy.

Impact:

iCell Neurons confirmed clinical findings of a genetic link to the risk and severity of chemotherapeutic-induced neuropathy. These findings may provide basis for safer dosing of the widely used anticancer agent vincristine.

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.

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