Applications

iPS Cell Disease Modeling

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Disease in a Dish

The availability of donor-specific induced pluripotent stem (iPS) cells, coupled with gene-editing techniques and genome-wide association studies (GWAS), is enabling new insights into the molecular basis and mechanisms of human disease. To enable you to rapidly and reproducibly implement these cellular disease models, Cellular Dynamics provides cryopreserved iPSC-derived cell types that can be produced from a diverse bank of iPS cells comprised of diseased genotypes with introduced or corrected mutations, as well as donor cohorts.

What are the advantages of iPSC-derived cells?
  • Reproducible research: High purity and rigorous quality control to ensure the same performance with every batch
    By employing heavily qualified materials, optimized differentiation processes, and rigorous quality procedures, CDI manufactures cells that work the same every time, ensuring research can be replicated between wells, experiments, and labs.
  • Human relevance: More accurately mimic disease processes with species-specific results
    The large number of drug candidates that are effective in mice but not humans clearly demonstrates a gap between animal models of disease and clinical translation. While animal models of disease offer some advantages, such as the ability to observe behavioral phenotypes, CDI’s iPSC-derived human cells provide physiologically relevant disease models, overcoming potential species-specific differences.
  • Rapid results: Get results faster with cryopreserved cells. Just thaw, plate, and assay
    iPSC-derived cellular models can be difficult to implement due to laborious and lengthy differentiation protocols, e.g. ~4 weeks for dopaminergic neurons and even longer for astrocytes. CDI’s ready-to-use cells – just thaw, plate, and assay – can accelerate your research by enabling you to complete more experiments in less time.
  • Choice in genetic background: Differentiated cells available from a diverse collection including diseased lines and isogenic controls
    CDI is engaged in several large-scale iPS cell reprogramming and banking projects making iPS cells and their differentiated progeny broadly available from thousands of backgrounds representing typical human diversity and various disease states. Additionally, by introducing or correcting mutations, CDI is making isogenic controls available for diseased lines. Use our searchable database to quickly find iPSC-derived cells with specific disease mutations and their isogenic controls and avoid the lengthy processes of donor recruitment, reprogramming, and differentiation optimization.


How are diseases modeled with iPS cells?

Diseases are typically modeled in vitro in three ways:

  • Innate 
    iPS cells are generated from donors with specific genotypes and differentiated into cell types associated with the disease of interest. As a control, iPS cells from apparently healthy normal (AHN) donors are differentiated into the same cell type and phenotypic and functional analyses are compared. This approach is particularly helpful with diseases of unknown or complex genetic backgrounds. To find control lines for this approach, visit our iCell® portfolio consisting of cells differentiated from AHN donors. iPSC-derived cells from an extensive collection of donors with specific diseases are available in our MyCell® portfolio.
  • Engineered
    In cases where a specific mutation is known to be involved in a disease state, the engineered approach can be used to study the effect of the mutation in as precise a model as possible. Cells from either AHN or donors with a confirmed disease mutation can have that mutation edited with CRISPR technology to either introduce or correct the mutation, respectively. The two isogenic cell lines created can then be differentiated into the cell type of interest, with the single mutation being the sole variable being studied. iPSC-derived cells with specific disease mutations and their isogenic controls are available in our MyCell portfolio.
  • Induced
    In addition, a disease state can be induced by subjecting iPSC-derived cells from AHN donors to specific culture conditions. To view the cell types available from AHN donors, visit our iCell portfolio. For examples of how to induce a disease state through culture conditions, view our application protocols on modeling cardiac hypertrophy.

Figure 1: Three Approaches to Disease Modeling with Human iPS Cells

To learn more about the cutting-edge research using iPSC-derived disease models, see the applications, below.

Modeling Cardiac Hypertrophy

Cardiac hypertrophy can occur in response to various pathological stimuli and is characterized by cellular changes including reactivation of the fetal gene program, increases in cellular volume...

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Modeling Cardiac Hypertrophy

Discovery, Disease Modeling

Cardiac hypertrophy can occur in response to various pathological stimuli and is characterized by cellular changes including reactivation of the fetal gene program, increases in cellular volume, and reorganization of the cytoskeleton. Using CDI’s cardiomyocytes, researchers can induce the hypertrophic condition in vitro using stimuli, such as endothelin-1, and measured by phenotypic endpoints including:

  • BNP gene expression by qRT-PCR
  • BNP protein expression by flow cytometry
  • BNP protein expression by HCA
  • BNP protein secretion by ELISA

Modeling Hypoxia

Myocardial ischemia is a pathological condition characterized by reduced oxygen supply (hypoxia) that can lead to cell death, arrhythmia, organ injury, and death.

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Modeling Hypoxia

Discovery, Disease Modeling

Myocardial ischemia is a pathological condition characterized by reduced oxygen supply (hypoxia) that can lead to cell death, arrhythmia, organ injury, and death. Ironically, returning hypoxic myocardium to normoxic levels exacerbates the pathology (collectively known as myocardial reperfusion injury). CDI’s cardiomyocytes are amenable to hypoxia induction, measurement of hypoxia-induced functional endpoints, and screening for cardioprotective agents.

Modeling Diabetic Cardiomyopathy

Diabetic cardiomyopathy is a complication of type 2 diabetes that results from lifestyle and genetic conditions.

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Modeling Diabetic Cardiomyopathy

Discovery, Disease Modeling

Diabetic cardiomyopathy is a complication of type 2 diabetes that results from lifestyle and genetic conditions. CDI’s cardiomyocytes have been used to develop environmental and patient-specific in vitro models that recapitulate this complex metabolic condition. These models are employed in a phenotypic screening assay resulting in the identification of candidate protective molecules.

Modeling Hepatitis Infection

Hepatitis infection mediated by HCV and HBV is a common cause of liver disease and failure.

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Modeling Hepatitis Infection

Discovery, Disease Modeling

Hepatitis infection mediated by HCV and HBV is a common cause of liver disease and failure. Developing effective therapies for hepatitis has been limited due to the lack of physiologically relevant human disease models. CDI’s hepatocytes express hepatitis receptors (SR-B1, CD91, occludin, claudin-1), which support uptake and replication of clinically relevant hepatitis virus genotypes. These hepatocytes are being used in large-scale screens for novel therapeutic candidates. CDI offers hepatocytes from multiple donors including one with an IFNL4 function that does not readily clear HCV infection.

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.