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Acute & Chronic Cytotoxicity - Impedance Analysis

Gain detailed understanding of your compounds' acute and chronic cardiotoxic risks. Ncardia’s Impedance Service offers a real-time, label-free measurement of cardiotoxicity using human iPSC-derived cardiomyocytes. In addition to detecting acute drug effects, this assay reveals chronic cytotoxicity as well.


What are your benefits?

Evaluation of chronic compound effects
Enabled by non-invasive real-time data acquisition

Comprehensive
Benchmarking concentration- and time-dependent cardiac liabilities

Translatable
hiPSC-derived cardiomyocytes are a physiologically relevant model

Introduction

Because the cardiomyocyte contraction/relaxation cycle involves substantial changes in cell morphology and adhesion, it can be dynamically monitored using impedance. Impedance-based assays monitor short-term and long-term cell morphological changes, strength of cell attachment to multi-well plates, and contractility in a label-free and real-time manner, enabling better prediction of drug-induced cardiotoxicity.

The impedance analysis service is based on impedance monitoring of hiPSC-derived cardiomyocytes after compound treatment, followed by a thorough analysis by our in-house experts. Parameters analyzed comprise cardiomyocyte beat rate, impedance amplitude and beat rate regularity. In addition, the Cell Index (CI) is a reliable surrogate marker for cell viability.

Workflow

Case Study

Determining acute and long-term effects of anti-cancer drugs by impedance.

Many novel oncology therapeutics may induce cardiotoxicity by inhibiting survival pathways which are shared by both tumors and cardiac cells. As complex mechanisms underlie drug-induced toxicity, some compound effects will only become evident after longer incubation times. Impedance monitoring of hiPSC-derived cardiomyocytes enables a longer-time measurement of potential cardiotoxic drug effects in vitro.

Case study specifications

Cell type

Pluricyte® Cardiomyocytes

Format

48 wells
Technology xCelligence CardioECR (ACEA)

Assay window

Acute (30 min) till long-term (64h) effect

Assay controls

0.1% DMSO (vehicle control)

Test compounds

nilotinib, lapatinib, doxorubicin, and ponatinib

Compound concentrations

10 µM, 3 µM, 0.3 µM

Parameters

IBD10 (beat duration defined as the width at 10% of the CI amplitude)

CI amplitude

Beat rate

 

Results

The effects of 3 µM lapatinib, 3 µM nilotinib, 0.1 µM nitrendipine and 0.3 µM doxorubicin on the IBD10, CI amplitude and beat rate of Pluricyte® Cardiomyocytes were quantified at 30min., 24hr. and 64hr. post-addition. Data are shown as percentage change from baseline and are corrected for the negative control, 0.1% DMSO. Whereas addition of Nilotinib and Nitrendipine showed acute effects after compound addition, Lapatinib and Doxorubicin only exhibited a long-term toxic effect.

Effects of lapatinib, nilotinib, nitrendipine and doxorubicin on the IBD10, CI amplitude and beat rate of Pluricyte Cardiomyocytes

 

Conclusion

Impedance measurements allows for a simultaneous assessment of short-term and long-term drug-induced cardiotoxicity from a single well, leading to better prediction of drug-induced cardiotoxicity.

Interested?

Would you like to know more about our Impedance Service, or any of our other services?

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