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Monitoring drug-induced cytotoxicity and hepatotoxicity using impedance

A number of different cell-based assays for cytotoxic effects of drugs exist including the lactate dehydrogenase (LDH) leakage assay, the neutral red assay, protein measurement and methyl tetrazolium (MTT) assay. We describe the development and optimization of a cell-based assay for cytotoxicity using impedance measurements. This assay is sensitive and provides reproducible results for safety pharmacology, toxicity screens of adherent, proliferating or non-proliferating cells. Changes in the impedance signal indicate effects on cell contractility, cell morphology and proliferation.

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In depth profiling of human iPSC cardiomyocytes: From electrophysiology to phenotypic assays

In depth profiling of human iPSC cardiomyocytes: From electrophysiology to phenotypic assays. Metrion’s Saïd El Haou presentation covers the topics of Manual Patch Clamp – Current Clamp, Axion Maestro – MEA and the Nanion CardioExcyte96 – Impedance.

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Modulation of voltage-gated calcium channels in disease

Presentation from the Metrion Biosciences’ external speaker series, Professor Gary Stephens, University of Reading, 28th November 2016.

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CiPA update: Refining in vitro cardiac ion channel assays, in silico models and iPSC cardiomyocyte reagents for improved proarrhythmia risk prediction

Metrion is working towards the requirements of the FDA’s Comprehensive in vitro Proarrhythmia (CiPA) initiative (cipaproject.org) which comprises 3 parts: 1) High quality in vitro cardiac ion channel assays, 2) Comprehensive in silico action potential (AP) models, and 3) Predictive assays using induced pluripotent stem cell derived cardiomyocytes (iPSC-CM).

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Human ventricular stem cell cardiomyocytes: validating in vitro assays and screening platforms for proarrhythmia risk prediction

To fulfil the last requirement of the CiPA initiative, the suitability and maturity of ventricular iPSC-CM need to be determined. In the current study, two ventricular iPSC- CM cell lines (LDN-1 and LDN-2) were generated and their molecular and biophysical properties compared with a commercial iPSC-CM cell line (COM-1) using three different methodologies.

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Electrophysiological profiling of Axiogenesis vCor.4U iPSC-derived cardiomyocytes

Here, we have assessed the suitability of Axiogenesis CorV.4U 2nd generation iPSC-CM for cardiotoxicity screening by evaluating their biophysical and pharmacological characteristics using three different methodologies:

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Human stem cell-derived cardiomyocytes: in vitro assays and screening platforms for exploring ventricular and atrial phenotypes

For CiPA, iPSC-CMs expressing a mature ventricular phenotype are required. At Metrion Biosciences we have focused on electrophysiological profiling of Axol Human iPSC-Derived Ventricular Cardiomyocytes (hiPSC-vCMs) by evaluating their biophysical and pharmacological characteristics.

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CiPA update: in vitro cardiac ion channel screens, in silico models and stem cell iPS cardiomyocyte assays for proarrhythmia risk prediction

Presentation by Marc Rogers (Metrion CSO) at the June 2016 Sophion Ion Channel Modulation Symposium, Clare College, Cambridge (UK). CiPA update: in vitro cardiac ion channel screens, in silico models and stem cell iPS cardiomyocyte assays for proarrhythmia risk prediction.

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Profiling endogenous sodium channels in the ND7-23 neuroblastoma cell line: implications for use as a heterologous ion channel expression system and native tissue model suitable for automated patch-clamp screening

Voltage-dependent sodium channels (Nav) are implicated in a wide range of diseases, with their role in triggering and modulating membrane excitability making them key drug discovery targets for cardiac and neurological indications. Neuronal Nav’s are divided into TTX-sensitive (Nav1.1, Nav1.2, Nav1.3, Nav1.6 and Nav1.7) and TTX-resistant channels (Nav1.8 and Nav1.9), with those found in the CNS underlying various types of epilepsy and those expressed in the periphery implicated in many types of pain behaviour such as inflammatory, neuropathic, chemotherapy and cancer-induced pain, as well as visceral pain conditions such as irritable bowel syndrome (IBS). 

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Using high quality HTS automated patch-clamp data from human cardiac ion channels and in silico action potential modelling to cost-effectively predict QP prolongation and arrhythmia risk for CiPA

Presentation by Marc Rogers (Metrion CSO) at the September 2015 Safety Pharmacological Society, Prague. Using high quality HTS automated patch-clamp data from human cardiac ion channels and in silico action potential modelling to cost-effectively predict QP prolongation and arrhythmia risk for CiPA.

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