Cellular Dynamics | Product Pipeline

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.

Click image to run a video showing beating iCell Cardiomyocytes.


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 online or contact Cellular Dynamics:

+1 (608) 310-5100 | US toll-free (877) 310-6688

	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: Cytotoxicity Characterization (PDF)

Application Notes	Assaying Cell Viability (PDF)

	Assaying Cytotoxicity (PDF)

	Assaying Caspase Activity & Apoptosis (PDF)

	Assaying Mitochondrial Membrane Potential (PDF)

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

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

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

Bibliography	Published Research (HTML)

Posters	Human Induced Pluripotent Stem Cell Derived Cardiomyocytesfor Assessing Drug-induced Cardiac Arrhythmias (PDF, presented at SOT Annual Meeting 2011)

	Assessment of drug-induced prolongation in human induced cardiomyocytes using Microelectrode Arrays (PDF, presented at SOT Annual Meeting 2010)

	Characterization Of Cardiac Channel Function In Human Induced Pluripotent Stem Cell-derived Cardiomyocytes Using Automated and Manual Patch Clamp Techniques (PDF, presented at SOT Annual Meeting 2010)

	Characterization of Induced Pluripotent Stem Cell-derived Cardiomyocytes and Their Industrialized Production for Use in Drug Discovery and Toxicity Testing (PDF, presented at WPC 2010)

	Induced Pluripotent Stem (iPS) Cell-derived Cardiomyocytes and Multivariate Analysis for Detection of Potential QT Perturbation (PDF, presented at SPS 2009)

	Industrialized Production of Human iPS Cell-derived Cardiomyocytes (PDF, presented at SBS Screening Stem Cells 2009)

	Large Scale Production and Characterization of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes for Use in Assessing Cardiotoxicity (PDF, presented at SBS 2010)

	Profiling Compounds with Cardiotoxic Potential Using High Content Imaging in Rat H9C2 Cells and Human Induced Pluripotent Stem Cell-derived Cardiomyocytes (PDF, presented at SOT Annual Meeting 2010)

	The Technical Merits Required to Develop High Content Imaging Applications for Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells (PDF, presented at SOT Annual Meeting 2010)

User Documentation


User's Guide	iCell Cardiomyocytes (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