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iCell^® Cardiomyocytes

iCell Cardiomyocytes and Media

Cellular Dynamics introduces iCell^® Cardiomyocytes, human induced pluripotent stem (iPS) cell-derived cardiomyocytes. These human cardiac cells are specifically designed to 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.

Specs
Advantages
Applications
Ordering
Support
Literature

Specifications

Cellular Dynamics International's iCell^® Cardiomyocytes are highly purified human cardiomyocytes derived from iPS cells through CDI's proprietary differentiation and purification protocols. The cells express monomeric red fluorescent protein (mRFP) and blasticidin resistance, both of which are under the control of the alpha-myosin heavy chain (Myh6) promoter that allows simultaneous cardiomyocyte purification and identification.

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.


Cell Type	Cardiomyocytes

Catalog #	CMC-100-110-001: 1 unit per vial; contains monomeric red fluorescent protein (RFP) expressed under control of the endogenous Myh6 promoter CMC-100-110-005: 5 units per vial; contains monomeric red fluorescent protein (RFP) expressed under control of the endogenous Myh6 promoter CMC-100-010-001: 1 unit per vial; no RFP expression CMC-100-010-005: 5 units per vial; no RFP expression

Organism	Human

Source	Differentiated from CDI-MRB, a CDI-derived human iPS cell line

Sub-type	Pan-cardiac

Quantity	>1.5M platable cells / unit

Shipped	Frozen

Storage	Liquid nitrogen

Growth Properties	Adherent

Media	iCell Cardiomyocytes Plating Medium iCell Cardiomyocytes Maintenance Medium Media supplied with order; quantities sufficient for 2 weeks of cell culture

Advantages


Human Cells	Because cardiac tissue shows species-specific protein expression patterns, use of terminally differentiated human cardiomyocytes, rather than other surrogate models (cadaveric or animal cells as well as transformed immortalized cells lines), for drug discovery and toxicity testing is expected to generate results that more accurately predict the relevant in vivo human response. Therefore, use of iCell Cardiomyocytes saves valuable time, resources, and compound. iCell Cardiomyocytes are differentiated from human pluripotent stem cells, maintained in vitro, and thus provide an easily accessible and physiologically relevant model system for assessing compound effects on human cardiac cellular electrophysiology.

Highly Pure Cell Population	Provides cardiac-specific response to reference molecules.

Homogenous and Reproducible	iCell Cardiomyocytes are available in sufficient homogenous quantities and demonstrate typical human cardiomyocyte behavior and responses, and are highly amenable for carrying out reproducible dose and time experiments

Fully Functional Model	iCell Cardiomyocytes exhibit standard biochemical and electrophysiological characteristics of normal human heart cells, forming electrically connected syncytial layers that beat in synchrony, with a demonstrated utility in numerous biochemical assays and arrhythmia testing.

Easy to Implement	Cells are shipped as cryopreservedsuspensions of dissociated cells with iCell Cardiomyocytes Plating Medium and iCell Cardiomyocytes Maintenance Media, specially formulated for optimal cell performance. Simply thaw and use.

Acute and Longer-term Testing	iCell Cardiomyocytes remain viable in culture for up to two weeks, thus enabling assessment of both acute and longer-term toxicity testing.

iPS Cell-derived	iCell Cardiomyocytes are differentiated from iPS cells reprogrammed from a non-embryonic terminally differentiated cell type, thus avoiding the controversial and ethical issues surrounding embryonic stem cell use.

Applications

Types of Applications

iCell Cardiomyocytes have demonstrated utility in numerous biochemical and electrophysiological assays for use in toxicology, safe pharmacology, drug discovery, and basic life science research.

Cell-based Assays

Cell viability
Apoptosis
ATP production
Oxidative stress
Mitochondrial dysfunction

Electophysiological Applications

Conventional patch clamp recording
Microelectrode assay (MEA) recording

Cell-based Assay Data

Figure1: Typical cardiotoxic responses
iCell cardiomyocytes were plated into 96-well plates and then treated with increasing concentrations of the listed cardiotoxic agents. The graphs illustrate the dose-response relations between the tested compound and (A) viability (ATP levels), (B) apoptosis (caspase 3/7 activity), and (C) mitochondrial dysfunction (membrane potential). iCell Cardiomyocytes demonstrated concentration dependent effects over all assays.

Electrophysiological Application Data

Cardiac action potentials are the rhythmic electrical oscillation of the cardiomyocyte membrane potential. Action potentials underlie basic cardiac function and arise through the precise activity of ion channels located in the plasma membrane. Small molecule compounds can disrupt the functionality of these ion channels, particularly the human ether a' go-go (hERG) channel, which carries the rapidly activating delayed rectifier potassium current (I_Kr). Cardiac ion channel dysfunction can lead to prolonged action potential duration, ventricular arrhythmias, and even sudden death. iCell Cardiomyocytes exhibit characteristics and electrophysiological responses of native human cardiac tissue. The electrical activity and controllable environmental conditions of these cardiomyocytes provide an ideal model for arrhythmia testing.

Ephys Data

Figure 2: Example Action Potential Recording and Pharmacological Responses of Isolated iCell Cardiomyocytes
Spontaneous action potentials were recorded from an iCell Cardiomyocyte using the whole-cell, current clamp technique. The upper tracing illustrates an action potential train recorded while being perfused with Tyrode's saline (basal), 10 nM of the I_Kr blocker E-4031, or 10 μM of the calcium channel blocker nifedipine. The lower groups of tracings illustrate (A) normal action potentials during exposure to Tyrode's saline, (B and C) prolonged action potentials and early after depolarizations (EADs) in the presence of 10 nM E-4031, (D and E) recovery following washout, and (F) the resumption of spontaneous activity following nifedipine washout.

To Order

Request a quote or contact Cellular Dynamics:
+1 (608) 310-5100 | US toll-free +1 (877) 310-6688

In Japan, contact IPS Academia Japan:
+81 75 256-8582

	Units per Vial	Catalog #

iCell Cardiomyocytes^ (includes iCell Cardiomyocytes Plating and Maintenance media)	1 5 1 5	CMC-100-110-001⁺ CMC-100-110-005⁺ CMC-100-010-001* CMC-100-010-005*

iCell Cardiomyocytes Maintenance Medium	1 5	CMM-100-120-001 CMM-100-120-005

^ >1.5M platable cells per unit ⁺ Contains monomeric red fluorescent protein (RFP) expressed under control of the endogenous Myh6 promoter * No RFP expression

Support


Training	Prior to handling iCell Cardiomyocytes, watch the video Handling iCell Cardiomyocytes for proper handling techniques. To receive advanced, in-laboratory education on the use of iCell products, sign up for CDI's iCertification Program.

Frequently Asked Questions	See the list of FAQs here.

Technical Support	Call +1 (608) 310-5100 \| US toll-free (877) 310-6688 or submit your technical question online.

Literature

Reference Materials
User Documentation
Technology Overview

Reference Materials


Datasheet	iCell Cardiomyocytes (PDF)

Application Notes	Add-Mix-Read Assays for Assessing Cell Health Using an iPSC-derived Cardiomyocyte Cell Model (HTML)

	Applying Transfection Technologies to Create Novel Screening Models (PDF)

	Assaying Caspase Activity & Apoptosis (PDF)

	Assaying Cell Viability (PDF)

	Assaying Cytotoxicity (PDF)

	Assaying Mitochondrial Membrane Potential (PDF)

Whitepapers	Induced Pluripotent Stem Cell (iPSC) Technology Facilitates Quick and Early Failure of Toxic or Ineffective NCEs (PDF)

	Use of Pluripotent Stem Cell-derived Cardiomyocytes to Understand Mechanisms of Cardiotoxic Compounds (PDF, Promega Cell Notes, Issue 23)

Presentations	Induced Pluripotent Stem Cell-derived Tissues and their Role in Developing Novel Assays for Drug Discovery (PDF, presented at AIMBE 2013)

	Human Induced Pluripotent Stem Cell Derived Cardiomyocytes Are a More Relevant Model Than H9C2 Cells for Assessing Mitochondrial Function in Drug Discovery and Toxicity Screens (PDF, presented at SLAS2013)

	Quantification of Cardioactive Drug Effects Using xCELLigence RTCA Cardio and Human iPS-derived Cardiomyocytes (Audio, presented at SOT Annual Meeting 2013)

	What Makes a Cardiomyocyte a Cardiomyocyte? (PDF, presented at HESI 2013)

	Application of iPS Cell-derived Cells and a Novel Electrophysiology Platform for Neuronal and Cardiac Toxicity Evaluation and Drug Screening (PDF, presented at SLAS2013)

	Advanced Assays for In Vitro Toxicity Evaluation and Phenotypic Screening (PDF, presented at SLAS2013)

	Advancements in the Use of iPS Cell-derived Cells for In Vitro Disease Modeling and Phenotypic Screening (PDF, presented at SLAS2013)

	Human iPS Cell Technology in Predictive and Mechanism-based Drug Discovery and Toxicity Testing Using Photometric-Based Assays (PDF, presented at SOT Annual Meeting 2012)

	Novel Assays for Drug Discovery and Toxicology Using Human iPS Cell-derived Neurons and Cardiomyocytes (PDF, presented at SLAS2012)

	Large-Scale Production of Human iPS Cell-derived Cardiomyocytes (Flash Video, MP3, Audio Podcast, presented ACT Annual Meeting 2009)

	Predictive Analysis of Cell Viability, Apoptosis and ADME/Tox Properties Using Multiparametric in vivo Assays and Human Induced Pluripotent Stem (iPS) Cell-derived Cardiomyocytes and Hepatocytes (PDF, presented at SOT Annual Meeting 2011)

	Predictive Multiparametric in vitro Assay Combinations for Cytotoxicity, Viability, Apoptosis, and ADME Applications with Hepatocytes and Human Stem Cell-derived Cardiomyocytes (Flash Video, MP3, Audio Podcast, presented at SOT Annual Meeting 2010)

	Stem Cell Toxicology and Drug Discovery: iCell Cardiomyocytes plus Molecular Devices Screening Platforms (WebEx Recording)

	Toxicology in the 21st Century: Stem Cells in Drug Discovery and Development (Flash Video, MP3, Audio Podcast, presented at SOT Annual Meeting 2010)

Bibliography	Published Research (HTML)

Posters	Application of Human iPS Cell-derived Models for Highly Predictive Toxicity Screening (PDF, presented at ELRIG 2013)

	Development and Characterization of Human Induced Pluripotent Stem Cell-Derived Model Systems for Muscular Dystrophy Disease Modeling and Drug Development (PDF, presented at the MDA 2013 Conference)

	iCell^® Cardiomyocytes: Human iPSC-derived Cardiomyocytes for Fully Functional and Comprehensive Assessments of NCE-mediated Effects. (PDF, presented at HESI 2013)

	Multiparameter In Vitro Assessment of Drug Effects on Cardiomyocyte Physiology Using iPS Cells (PDF, presented at SOT Annual Meeting 2013)

	Optical Measurements of Electrical Activity from hiPSC-derived Cardiomyocytes Is a Robust and High-throughput Method for Measuring NCE-effects on the Cardiac Action Potential (PDF, presented at SOT Annual Meeting 2013)

	Applications Development at CDI: Improving Workflows, Pushing Biology, and Enabling Screening (PDF, presented at the CDI User Group Meeting 2012)

	Human iPSC-derived Cells for Modelling Cellular Bioenergetics: Building a Metabolic Profile Using the XF Mito Stress Test (PDF, presented at the CDI User Group Meeting 2012)

	Advancements in the Use of iPS Cell-derived Systems for In Vitro Disease Modeling and Phenotypic Screening (PDF, presented at StemCONN 2013)

	Implementation of Human iPSC-derived Cell Types Into High Throughput Screening Workflows (PDF, presented at SLAS 2013)

User Documentation


User's Guide	iCell Cardiomyocytes (PDF)

Application Protocols	Immunofluorescent Labeling (PDF)

	Modeling Cardiac Hypertrophy: Endothelin-1 Induction with ELISA Analysis (PDF)

	Modeling Cardiac Hypertrophy: Endothelin-1 Induction with Flow Cytometry Analysis (PDF)

	Modeling Cardiac Hypertrophy: Endothelin-1 Induction with High Content Analysis (PDF)

	Modeling Cardiac Hypertrophy: Endothelin-1 Induction with qRT-PCR Analysis (PDF)

	Multielectrode Array System (PDF)

	Performing Perforated Patch Clamp (PDF)

	Total RNA Extraction (PDF)

	Using Transfection for siRNA Delivery (PDF)

	xCELLigence RTCA Cardio System (PDF)

	XF96 Extracellular Flux Analyzer (PDF)

Material Safety Data Sheets (MSDS)	iCell Cardiomyocytes (PDF)

	iCell Cardiomyocytes Plating Medium (PDF)

	iCell Cardiomyocytes Maintenance Medium (PDF)

Technology Overview


Datasheet	Cellular Dynamics International: True Human Biology in a Dish (PDF)

Poster	Reprogramming Human Peripheral Blood Cells (PDF, presented at ISSCR 2009)

Bibliography	Published Research (HTML)

iCell® Cardiomyocytes