iCell Cardiomyocytes

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iCell™ Cardiomyocytes

iCell Cardiomyocytes 24 hours after plating

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.

Product Description

Cellular Dynamics International’s (CDI) 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.

iCell Cardiomyocytes: Product Specifications

Cell Type	Cardiomyocytes

Catalog #	Unit size 1X:CMC-100-110-001 Unit size 5X: CMC-100-110-005

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

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

Advantages of iCell Cardiomyocytes


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.

Assays

iCell Cardiomyocytes have demonstrated utility in numerous biochemical and electrophysiological assays including (but not limited to):

Cell-based Assay Applications such as

Cell viability
Apoptosis
ATP production
Oxidative stress
Mitochondrial dysfunction

Electophysiological Applications such as

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 Tyrodes saline (Basal), 10nM of the I_Kr blocker E-4031, or 10μM of the calcium channel blocker Nifedipine. The lower groups of tracings illustrate A) normal action potentials during exposure to Tyrodes saline; B and C) prolonged action potentials and early after depolarizations (EADs) in the presence of 10nM E-4031; D and E) recovery following washout; and F) the resumption of spontaneous activity following Nifedipine washout.