Application of Human iPS Cell-Derived Models for Highly Predictive Toxicity Screening

11 Sept 2013

This poster presents the development of an industrial-scale manufacturing platform for the production of terminally-differentiated, human iPS cell-derived tissue types (e.g. neurons, cardiomyocytes, and hepatocytes) that are highly pure (>95%) and exhibit normal genotypic, phenotypic, and functional characteristics of native cells.

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iCell Neurons
Cellular Dynamics International
iCell® Neurons, derived from human induced pluripotent stem (iPS) cells, provide a unique in vitro system for preclinical drug discovery, neurotoxicity testing, predictive disease modeling, and basic cellular research. A better and more biologically relevant alternative to current cell models, iCell Neurons offer researchers access to commercial quantities of high quality, highly pure human neurons that possess typical phenotypic characteristics and functional of mature neurons. iCell® Neurons are a mixture of post-mitotic neural subtypes, comprised primarily of GABAergic and glutamatergic neurons, with typical physiological characteristics and functions. These cells quickly assume a typical neuronal morphology with branching neurites. In addition, iCell Neurons display a stable adherent single-cell morphology and remain viable for an extended culture period (≥14 days), making them amenable to a variety of electrophysiology, neurotoxicity, and synaptic neurotransmission assays. iCell® Neurons are shipped as cryopreserved suspensions of dissociated cells with specifically formulated culture media. Once thawed, iCell Neurons remain viable for extended culture periods, allowing for acute and chronic studies. iCell® Neurons Benefits: Human Cells - Saves valuable time, resources, and compound. Highly Pure Cell Population - Provides cardiac-specific response to reference molecules. Homogenous and Reproducible Fully Functional Model Acute and Longer-term Testing - Remain viable in culture for up to two weeks. iPS Cell-derived iCell® Neurons Applications: Cell-based Assays - Cell viability, Apoptosis, ATP production, Oxidative stress, Mitochondrial dysfunction. Electophysiological Applications - Conventional patch clamp recording, Microelectrode assay (MEA) recording.
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iCell Hepatocytes
Cellular Dynamics International
iCell® Hepatocytes, derived from human induced pluripotent stem (iPS) cells, provide access to commercial quantities of high quality, high purity human liver cells for preclinical drug discovery, hepatotoxicity testing, and disease research. iCell® Hepatocytes express alpha-1-antitrypsin (AAT), asialoglycoprotein receptor (ASGR1), hepatocyte nuclear factor 4 alpha (HNF4A), and secrete albumin at levels similar to adult primary human hepatocytes. In addition, the cells exhibit intrinsic metabolism (e.g. glycogen and lipid storage), xenobiotic metabolism, and transporter functions. Importantly, iCell Hepatocytes respond appropriately to known hepatotoxicants and support HCV and HBV infection. iCell® Hepatocytes are currently shipped as fresh cells, which remain viable and functional for at least 3 weeks following plating on collagen-coated plates. Thus, these cells can be used for acute and longer-term assays for targeted drug discovery, toxicity testing, and other life science research. iCell® Hepatocytes Benefits: Human Cells - Hepatocytes are terminally differentiated from human iPS cells and exhibit hepatocyte characteristics and functions. Homogenous and Reproducible Functionally Stable Known Genotype - Hepatocytes have been genotyped for 1,936 ADME markers in over 200 genes, including all FDA-validated genes and >90% of the ADME Core markers as defined by the PharmaADME group. iCell® Hepatocytes Applications: Heptatocytes are amenable to a variety of biochemical and cellular assays: Hepatoxicity, Intrinsic metabolism, Xenobiotic metabolism, Transporter function, Viral infectivity.
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iCell Endothelial Cells
Cellular Dynamics International
iCell® Endothelial Cells, interior surface blood vessel cells derived from human induced pluripotent stem (iPS) cells facilitate vascular-targeted drug discovery, tissue regeneration, and other life science research. iCell® Endothelial Cells exhibit characteristic endothelial gene and protein expression (e.g., CD31, CD105, CD144, ZO-1, and von Willebrand Factor) and endothelial cell functions (e.g., tubular formation, acetylated LDL uptake, barrier function, and wound healing). These cells are an ideal in vitro model system that provides a reliable source of endothelial cells suitable for use in vascular biology research including angiogenesis, atherosclerosis, inflammation, and many other research areas. iCell® Endothelial Cells are shipped as cryopreserved suspensions of dissociated cells with medium supplement, specially formulated for optimal cell performance. iCell Endothelial Cells remain viable in culture for up to 5 passages, thus enabling assessment of both acute and longer-term testing.iCell® Endothelial Cells Benefits: Human Cells - Cells are differentiated from human pluripotent stem cells that provide an easily accessible and physiologically relevant model system for vascular-targeted drug discovery, tissue regeneration and other vascular biology research. Highly Pure Cell Population - Provides endothelial cell-specific responses to reference molecules. Homogenous and Reproducible Fully Functional Model - Cells exhibit standard biochemical characteristics of normal human endothelial cells, and demonstrate utility in a variety of assays including cell migration, cytokine stimulation, tubular formation, and impedance/barrier function. Easy to Implement - Cells are shipped as cryopreserved suspensions of dissociated cells. Simply thaw and use. Acute and Longer-term Testing - Cells remain viable in culture for up to 5 passages, thus enabling assessment of both acute and longer-term testing. iPS Cell-derived iCell® Endothelial Cells Applications: Cells are amenable to a wide array of assays including: Cell adhesion, Cell invasion and migration, Cell permeability, Cell proliferation, Cell viability, Impedance/transendothelial electrical resistance, Tubular formation.
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iCell Cardiomyocytes
Cellular Dynamics International
iCell® Cardiomyocytes, human induced pluripotent stem (iPS) cell-derived cardiomyocytes, aid drug discovery and improve the predictability of drug efficacy and toxicity screens, weeding out ineffective and potentially toxic compounds early in the pharmaceutical pipeline process before significant time and resources have been invested. iCell Cardiomyocytes are a mixture of spontaneously electrically active atrial, nodal, and ventricular-like myocytes that possess typical electrophysiological characteristics and exhibit expected electrophysiological and biochemical responses upon exposure to exogenous agents. Thus, these cells are a reliable source of human cardiomyocytes suitable for use in targeted drug discovery, toxicity testing, and other life science research. iCell Cardiomyocytes are shipped as cryopreserved suspensions of dissociated cells with specifically formulated culture media for optimal cell performance. Once thawed, iCell Cardiomyocytes remain viable in culture for up to two weeks, allowing for acute and chronic studies. iCell Cardiomyocytes Benefits: Human Cells - Saves valuable time, resources, and compound. Highly Pure Cell Population - Provides cardiac-specific response to reference molecules. Homogenous and Reproducible Fully Functional Model Acute and Longer-term Testing - Remain viable in culture for up to two weeks. iPS Cell-derived iCell Cardiomyocytes Applications: Cell-based Assays - Cell viability, Apoptosis, ATP production, Oxidative stress, Mitochondrial dysfunction. Electophysiological Applications - Conventional patch clamp recording, Microelectrode assay (MEA) recording.
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Cell Lines Stem Cells and Primary CellsCell-Based AssaysCardiomyocytes HepatocytesNeuronsToxicity

iCell Endothelial Cells

Cellular Dynamics International

iCell® Endothelial Cells, interior surface blood vessel cells derived from human induced pluripotent stem (iPS) cells facilitate vascular-targeted drug discovery, tissue regeneration, and other life science research. iCell® Endothelial Cells exhibit characteristic endothelial gene and protein expression (e.g., CD31, CD105, CD144, ZO-1, and von Willebrand Factor) and endothelial cell functions (e.g., tubular formation, acetylated LDL uptake, barrier function, and wound healing). These cells are an ideal in vitro model system that provides a reliable source of endothelial cells suitable for use in vascular biology research including angiogenesis, atherosclerosis, inflammation, and many other research areas. iCell® Endothelial Cells are shipped as cryopreserved suspensions of dissociated cells with medium supplement, specially formulated for optimal cell performance. iCell Endothelial Cells remain viable in culture for up to 5 passages, thus enabling assessment of both acute and longer-term testing.iCell® Endothelial Cells Benefits: Human Cells - Cells are differentiated from human pluripotent stem cells that provide an easily accessible and physiologically relevant model system for vascular-targeted drug discovery, tissue regeneration and other vascular biology research. Highly Pure Cell Population - Provides endothelial cell-specific responses to reference molecules. Homogenous and Reproducible Fully Functional Model - Cells exhibit standard biochemical characteristics of normal human endothelial cells, and demonstrate utility in a variety of assays including cell migration, cytokine stimulation, tubular formation, and impedance/barrier function. Easy to Implement - Cells are shipped as cryopreserved suspensions of dissociated cells. Simply thaw and use. Acute and Longer-term Testing - Cells remain viable in culture for up to 5 passages, thus enabling assessment of both acute and longer-term testing. iPS Cell-derived iCell® Endothelial Cells Applications: Cells are amenable to a wide array of assays including: Cell adhesion, Cell invasion and migration, Cell permeability, Cell proliferation, Cell viability, Impedance/transendothelial electrical resistance, Tubular formation.

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Application of Human iPS Cell-Derived Models for Highly Predictive Toxicity Screening

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iCell Neurons

iCell Hepatocytes

iCell Endothelial Cells

iCell Cardiomyocytes

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