Applications

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Measuring Vascular Endothelial Cell Barrier Function

The endothelial cell barrier regulates the passage of materials and transit of blood cells into and out of the bloodstream.

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Measuring Vascular Endothelial Cell Barrier Function

Discovery, Toxicity

The endothelial cell barrier regulates the passage of materials and transit of blood cells into and out of the bloodstream. Thus, models of barrier function are relevant for the study of xenobiotic permeability, metastasis, inflammation, and wound healing. Endothelial cells’ barrier function and modulation by agents, such as thrombin, can be measured using impedance platforms (ACEA xCELLigence, Applied BioPhysics ECIS).

  1. Assaying Barrier Function. Cellular Dynamics Application Note.
  2. Assaying Barrier Function: xCELLigence RTCA Cardio System. Cellular Dynamics Application Protocol.

Measuring Neuronal Synaptic Activity

The measurement of neuronal synaptic activity can be accomplished through various signaling pathways.

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Measuring Neuronal Synaptic Activity

Discovery, Toxicity

The measurement of neuronal synaptic activity can be accomplished through various signaling pathways. These pathways can be measured in CDI’s neurons and dopaneurons using platforms including:

Measuring Neuronal Electrophysiology

The communication between neurons and between neurons and other cell types is accomplished through electrical signals.

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Measuring Neuronal Electrophysiology

Discovery, Regenerative Medicine, Toxicity

The communication between neurons and between neurons and other cell types is accomplished through electrical signals. CDI’s neurons exhibit biologically relevant electrical functions typical of primary human cortical neurons including evoked and spontaneous action potentials, inhibitory and excitatory post-synaptic currents, and ion channel pharmacology. These responses can be measured using platforms including:

Measuring Vascular Endothelial Cell Proliferation

The regulation of endothelial cell proliferation plays a fundamental role in vascular remodeling and angiogenesis in normal and pathological conditions.

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Measuring Vascular Endothelial Cell Proliferation

Discovery, Regenerative Medicine, Toxicity

The regulation of endothelial cell proliferation plays a fundamental role in vascular remodeling and angiogenesis in normal and pathological conditions. CDI’s endothelial cells exhibit a dose-dependent proliferation response to VEGF that is sensitive to inhibition by tyrphostin, a selective VEGF receptor inhibitor, as measured using the CellTiter-Glo Assay (Promega).

  1. Assaying Cell Proliferation. Cellular Dynamics Application Note.
  2. Belair D, Carlson C, et al. (2014) Label-free, Real-time Analysis of Endothelial Cell Morphogenesis Using iPSC-derived Endothelial Cells. Poster Presentation, AACR.

Modeling Varicella Zoster Virus Infection

CDI's neurons provide 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.

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Modeling Varicella Zoster Virus Infection

Discovery, Disease Modeling

CDI’s neurons provide 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. Specifically, VZV infection results in a non-productive infection characterized by viral gene expression in the absence of apoptosis. This disease phenotype enables molecular analysis of VZV-neuron interactions and mechanisms of VZV reactivation.

  1. Baird NL, Bowlin JL, et al. (2014) Varicella Zoster Virus DNA Does Not Accumulate in Infected Human Neurons. Virology 458-459:1-3.
  2. Baird NL, Bowlin JL, et al. (2014) Comparison of Varicella-Zoster Virus RNA Sequences in Human Neurons and Fibroblasts. J Virol 88(10):5877-80.
  3. Yu X, Sietz S, et al. (2013) Varicella Zoster Virus Infection of Highly Pure Terminally Differentiated Human Neurons. J Neurovirol 19:75-81.
  4. Grose C, Xiaoli Y, et al. (2013) Aberrant Virion Assembly and Limited Glycoprotein C Production in Varicella-Zoster Virus-Infected Neurons. J Virol 87(17):9643-8.

Modeling Botulinum Neurotoxin Infection

CDI's neurons provide a functionally relevant human model to measure Clostridium botulinum neurotoxin (BoNT) activity.

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Modeling Botulinum Neurotoxin Infection

Discovery, Disease Modeling, Toxicity

CDI’s neurons provide a functionally relevant human model to measure Clostridium botulinum neurotoxin (BoNT) activity. Compared with primary rat spinal cord cells, CDI’s neurons showed equal or increased sensitivity, improved dose-response, and more complete SNARE protein cleavage in response to BoNT treatment. CDI’s neurons are rapidly being adopted by researchers to study mechanisms of BoNT toxicity and by BoNT manufacturers to replace an expensive and labor-intensive mouse bioassay for potency testing.

Modeling Epilepsy

Epilepsy is a condition with recurring seizures caused by abnormal electrical activity in the brain.

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Modeling Epilepsy

Discovery, Disease Modeling

Epilepsy is a condition with recurring seizures caused by abnormal electrical activity in the brain. CDI’s neurons have been used to develop in vitro models that recapitulate the functional phenotype of pathogenic mutations. These models are being used to better understand the biophysical properties of ion channels with the goal of identifying candidate therapeutic molecules for improved drug safety.

  1. Padilla KM, Antonio BM, et al. (2014) Approaches to Understanding Human Ion Channel Genetic Variation and Disease – An Example with a KCNT1 Variant and Infantile Epilepsy Disorder. Poster Presentation, Society for Neuroscience.

Modeling Parkinson’s Disease

Parkinson's disease is the result of a progressing degeneration of dopamine-producing brain cells, specifically midbrain dopaminergic neurons, that results in a loss of motor function and in dementia.

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Modeling Parkinson’s Disease

Discovery, Disease Modeling

Parkinson’s disease is the result of a progressing degeneration of dopamine-producing brain cells, specifically midbrain dopaminergic neurons, that result in a loss of motor function and in dementia. CDI’s neurons and dopaneurons are being used to elucidate the mechanisms that underlie the pathogenesis of Parkinson’s disease including mitochondrial dysfunction, synapse degeneration, ubiquitin-proteasome degradation, oxidative stress, and others.

Modeling Alzheimer’s Disease

Alzheimer's disease (AD) is characterized by the neuropathological hallmarks of amyloid plaques and neurofibrillary tangles that eventually result in neuronal loss in the cerebral cortex and hippocampus.

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Modeling Alzheimer’s Disease

Discovery, Disease Modeling

Alzheimer’s disease (AD) is characterized by the neuropathological hallmarks of amyloid plaques and neurofibrillary tangles that eventually result in neuronal loss in the cerebral cortex and hippocampus. As functional human models, CDI’s neurons are actively being applied in research to investigate relevant molecular and cellular mechanisms of AD. These in vitro cellular models are capable of recapitulating the disease phenotype and have been employed in various assays including a high-throughput phenotypic screening assay resulting in the identification of candidate protective molecules.

  1. Chai X, Dage JL, et al. (2012) Constitutive Secretion of Tau Protein by an Unconventional Mechanism. Neurobiol Dis 48(3):356-366.
  2. 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(2):213-227.
  3. Maloney JA, Bainbridge T, et al. (2014) Molecular Mechanisms of Alzheimer’s Disease Protection by the A673T Allele of the Amyloid Precursor Protein. J Biol Chem 289(45):30990-1000.
  4. Alhebshi AH, Odawara A, et al. (2014) Thymoquinone Protects Cultured Hippocampal and Human Induced Pluripotent Stem Cells-derived Neurons against α-synuclein-induced Synapse Damage. Neurosci Lett 570:126-131.
  5. Carlson C, Wang J, et al. (2014) Characterization of an Isogenic Disease Model of Alzheimer’s Disease from Human iPSC-derived Neurons. Poster Presentation, Society for Neuroscience.
  6. Usenovic M, Niroomand S, et al. (2014) Model of Tau Pathology in Induced Pluripotent Stem Cell-derived Human Neurons. Poster Presentation, Society for Neuroscience.

Modeling Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a group of developmental disabilities including Rett and Asperger’s syndromes that result in significant social, communication, and behavioral challenges.

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Modeling Autism Spectrum Disorder

Discovery, Disease Modeling

Autism spectrum disorder (ASD) is a group of developmental disabilities that result in significant social, communication, and behavioral challenges. Model ASD using CDI’s iPSC-derived neurons, including those from donors with autism, Asperger’s, or cell types that display autistic-like phenotypes such as Rett syndrome knock-out model.

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