Mel.Cor - Cor.4U MEA Assay Service

Cells Cor.4U® Human iPS derived cardiomyocytes
Species Human
Cell source Human iPS cells of 26y/o Caucasian female
Cell format Monolayer of pure cardiomyocytes
Service type       Functional / phenotypic analysis
Delivery

 A study protocol will be sent to initiate the study. Results are sent as draft and final study report

Timeline

 Experimental run time: ~1.5 weeks per plate. Draft report: within 4 weeks.

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MelCor The Axion Meastro MEA can provide label free electrophysiological information in a 48 or 96 well assayThe Axion Meastro MEA can provide label free electrophysiological information in a 48- or 96-well assay.  Axiogenesis only uses cardiomyocytes that have been stringently lot-tested for MEA baseline activity and response to basic ion channel blockers. Here, the Na+ spike heat map shows those electrodes reaching a >2 mV threshold for detection from 6 different cardiomyocyte lots. Cor.4U cardiomyocytes produce extracellular field potentials with an electrocardiogram-like readout (i.e. QT interval surrogate).

 

ADVANTAGES 

  • Primary-like electrophysiology from cardiomyocytes of human origin
  • Non-invasive / label-free test system up to 96-well format
  • Predictive and relevant for cardiac safety pharmacology
  • Time- and cost-effective; Low amount of compound required

  

MelCor Example readout of 3 experimental parametersExample readout of 3 experimental parameters. E-4031 induces prolongation of the field potential duration (FPD) and Fridericia’s-corrected FPD at 30 and 100 nM. Amplitude of Na+ spike is also significantly inhibited at 30 and 100 nM.

 

Technology overview

Human Cor.4U® Mel.Cor® is an in vitro and non-invasive assay system to monitor Axiogenesis' Cor.4U® human induced pluripotent stem (iPS) cell-derived cardiomyocytes by means of extracellular field potential recordings from microelectrode arrays (MEA).

 

MelCor Baseline reproducibility among CiPA test sites using Cor.4U on the Axion MaestroBaseline reproducibility among CiPA test sites using Cor.4U® on the Axion Maestro.  Analysis of different electro-physiological parameters by testing site (left). Pharmacological analysis. Comparison of different testing sites per compound.MelCor Baseline reproducibility among CiPA test sites using Cor.4U on the Axion Maestro (right).

 

The Cor.4U® human iPS cell-derived cardiomyocytes reveal electrophysiological properties typical for human cardiac myocytes like functional Na+, Ca2+, and K+ voltage-gated ion channels including the hERG channel and their correct modulation through e.g. ß-adrenergic or muscarinic receptors.

The combination of the Cor.4U® human cardiomycoytes with the Mel.Cor® MEA assay provides an ideal tool to assess pharmacological, safety pharmacological and toxicological effects of drug candidates on human cardiomyocytes.

Effects of substances from different compound classes tested:

Compound class

Drug

(application)

Effect conc. (µM)

hSC-CM

IKr blocker

 

E-4031

(Class III antiarhythmic)

10 nMfAPD+

250 nM; IB

Cisapride

(Prokinetic)

100 nM; fAPD+

1 µM; IB

Dofetilide

(Class III antiarhythmic)

10 nM, fAPD+

INa blocker

Tetrodotoxin (TTX)

(Neurotoxin)

1 - 10 µM; NC and SD+

ICa,L blocker

Nifedipine

(Anti-hypertensive)

100 nM; fAPD-

1000 nM; BA

Verapamil

(Anti-hypertensive)

0.1 µM fAPD-

1- 10 µM BA

ß-adrenergic receptor agonist

Isoproterenol

(Bronchodilator)

1 - 10 nM; PC

α-adreneric  

receptor agonist

Phenylephrine

(Vasoconstrictor)

100 nM; PC

Table 1: Abbreviations: NC - negative chronotropic, PC - positive chronortropic, fAPD+ - fAPD prolongation, fAPD- -fAPD shortening, IB - irregular beating, BA - beating arrest, SD+ - slope duration prolongation

 

Advantages Cor.4U MEA

  • Primary-like cardiomyocytes of human origin.
  • Non-invasive test system.
  • Predictive and relevant for cardiac safety pharmacology.
  • Low amount of compound required.

FIND US

Nattermannallee 1, Bldg S20
50829 Cologne
Germany –  (Map)

600 W Germantown Pike, Suite 110
Plymouth Meeting, PA 19462
USA – (Map)

EMAIL US

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+49 221 99 88 18-0

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+1 844-511-6959

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