Cardiac Translational Manual Patch Assays
Metrion offers a set of reliable and reproducible translational human cardiovascular assays to demonstrate the cardiac safety of your therapeutic compounds in line with current and future CiPA and FDA guidelines.
High quality cardiac toxicity data generation and interpretation is vital to the efficient progression of a drug discovery campaign. Metrion offers a range of translational, phenotypic cardiac assays and platforms that have been validated using a number of commercially available human iPSC-derived cardiomyocyte cell lines. Using technologies such as manual patch clamp electrophysiology, multi-electrode array (MEA; Maestro platform) or dual MEA/impedance readouts (CardioExcyte96), Metrion can offer a direct readout of physiological function and cardiac risk in the iPSC-derived cardiomyocyte cell line- of your choosing.
Manual Patch Assays
Metrion has considerable expertise working with human iPSC-derived cardiomyocytes on the manual patch clamp platform. The company has access to, and has characterised, a wide range of commercially available cell lines from a number of vendors. Metrion offers services to screen compounds against action potentials and membrane currents recorded from iPSC-derived cardiomyocytes. Furthermore, we provide a cell line characterisation service for companies and vendors looking to commercialise their cell lines.
Stimulated Action Potentials
Stable action potential recordings can be taken for up to one hour using stimulation via a bath field electrode or current injection through the recording pipette. These long-term recordings enable application of multiple concentrations of a compound during a single experiment (see panel below). Frequency-dependent effects on action potential parameters can also be investigated in this assay format.
CiPA Toolbox Compounds
Our testing of CiPA toolbox compounds can help identify and quantify the roles of key cardiac ion channels underlying the action potential in human cardiomyocytes, and thus to benchmark the effects and cardiac risk profile of new test compounds. For example, exposure to the hERG inhibitor dofetilide results in action potential prolongation, arrhythmogenesis and early after depolarisations (EADs), validating the proarrhythmic effect of a Torsadogenic compound in our in vitro assays.
Spontaneous Action Potential Recordings
iPSC-derived cardiomyocytes possess intrinsic pacemaker activity, resulting in spontaneous action potential firing. This allows us to determine the effect of a test compound on action potential firing frequency and to identify compounds with the potential to slow (bradycardia) or increase (tachycardia) heart rate in vivo. Metrion has tested a toolbox of compounds with cardiac activity and confirmed their anticipated effect on spontaneous action potential parameters, which were consistent with those determined from stimulated cells. For example, the hERG blocker dofetilide significantly prolonged the action potential duration of iPSC-derived cardiomyocytes and induced EADs (see Figures below).
Voltage Clamp Assays
Metrion has validated voltage clamp assays to quantify activity of a range of ion channels expressed in iPSC-derived ventricular and atrial cardiomyocytes. Metrion can determine the expression density of such currents as part of an in-depth service to characterise new cell lines. Voltage clamp studies using either iPSC-derived cardiomyocytes or cell lines expressing recombinant ion channels can also be used to support phenotypic and modelling predications as part of an integrated CiPA approach.
Translational Cardiac Assays Resource Library
- The Changing Landscape of Cardiac Safety
- Improving biological tools for disease modelling and drug discovery: Human iPSC-derived Atrial Cardiomyocytes
- vCor.4U™ Ventricular Enriched Cardiomyocytes: Pharmacological characterisation utilising manual patch clamp
- In depth profiling of human iPSC cardiomyocytes: From electrophysiology to phenotypic assays. Presentation by Metrion Biosciences’ Said El Haou, Ncardia Workshop, Cologne, 29th November – 1st December 2017.
- Development of an Impedance Based Screening Assay for Cardiac Safety and Cardiotoxicity Detection in Stem Cell derived Cardiomyocytes. Safety Pharmacology Society Annual Meeting, Barcelona, 2019
- Metrion Biosciences: high quality ion channel drug discovery service provider. Milner Therapeutics Symposium, Cambridge, 2019
- Assessment of human induced pluripotent stem cell-derived cardiomyocytes for evaluating drug-induced arrhythmias with multi-electrode array. Safety Pharmacology Society meeting, Washington DC, USA 2018.
- Functional characterisation of human iPSC-derived atrial cardiomyocytes. SelectBio Stem Cells and Antibodies in Drug Discovery, Cambridge, May 2018.
- Refining in vitro QPatch cardiac ion channel QPatch and MEA iPSC cardiomyocyte assays for CiPA. SOT San Antonio 2018 poster Late Breaking 12: Safety Assessment: Pharmaceutical and Non-Pharmaceutical.
- Comprehensive Profiling of Axiogenesis Ventricular vCor.4U iPSC-Derived Cardiomyocytes – From Electrophysiology to Phenotypic Assays. SPS Berlin 2017 poster 175.
- Differentiation and Validation of Human iPSC-Derived Atrial Cardiomyocytes. SPS Berlin 2017 poster 176.
- Electrophysiological Characterisation of Cellular Dynamics International Ventricular iCell2 iPSC-Derived Cardiomyocytes. SPS Berlin 2017 poster 177.
- Monitoring drug-induced cytotoxicity and hepatotoxicity using impedance. Advances in Cell Based Screening, Gothenburg, May 2017.
- Human ventricular stem cell cardiomyocytes: validating in vitro assays and screening platforms for proarrhythmia risk prediction. SPS Vancouver September 2016 poster 0242.
- Human stem cell-derived cardiomyocytes: in vitro assays and screening platforms for exploring ventricular and atrial phenotypes. SPS Vancouver September 2016 poster 0247.
- Electrophysiological profiling of Axiogenesis CorV.4U iPSC-derived cardiomyocytes. Axiogenesis Workshop Cologne September 2016.
- Atrial‐like cardiomyocytes from human pluripotent stem cells are a robust preclinical model for assessing atrial‐selective pharmacology
Let’s work together
What are your specific ion channel screening requirements?
If you have any questions, or would like to discuss your project, we will put you directly in touch with a member of our scientific team. Contact us today to discover more.