Abstract
Impedance-based measurement is a useful tool for assessing the contractility of plated cardiomyocytes in the context of early preclinical cardiosafety assessment. Induced pluripotent stem cell-derived cardiomyocytes (iPSCs) can be used for this purpose as these cells display similar electrochemical properties to primary cardiomyocytes and beat reliably and in synchronicity in culture. Here we describe a method for measuring the contractility of iPSCs using the xCELLigence RTCA impedance measurement system.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Shah RR (2005) Drugs, QT interval prolongation and ICH E14: the need to get it right. Drug Saf 28(2):115–125
Stevens JL, Baker TK (2009) The future of drug safety testing: expanding the view and narrowing the focus. Drug Discov Today 14(3–4):162–167
Brown AM (2005) HERG block, QT liability and sudden cardiac death. Novartis Found Symp 266:118–131; discussion 131–135, 155–158
Fermini B, Fossa AA (2003) The impact of drug-induced QT interval prolongation on drug discovery and development. Nat Rev Drug Discov 2(6):439–447
Valentin JP, Bialecki R, Ewart L, Hammond T, Leishmann D, Lindgren S, Martinez V, Pollard C, Redfern W, Wallis R (2009) A framework to assess the translation of safety pharmacology data to humans. J Pharmacol Toxicol Methods 60(2):152–158
Denning C, Anderson D (2008) Cardiomyocytes from human embryonic stem cells as predictors of cardiotoxicity. Drug Discov Today: Ther Strateg 5(4):223–232
Ma J, Guo L, Fiene SJ, Anson BD, Thomson JA, Kamp TJ, Kolaja KL, Swanson BJ, January CT (2011) High purity human-induced pluripotent stem cell-derived cardiomyocytes: electrophysiological properties of action potentials and ionic currents. Am J Physiol Heart Circ Physiol 301(5):H2006–H2017
Nguemo F, Saric T, Pfannkuche K, Watzele M, Reppel M, Hescheler J (2012) In vitro model for assessing arrhythmogenic properties of drugs based on high-resolution impedance measurements. Cell Physiol Biochem 29(5–6):819–832
Harris K, Aylott M, Cui Y, Louttit JB, McMahon NC, Sridhar A (2013) Comparison of electrophysiological data from human-induced pluripotent stem cell-derived cardiomyocytes to functional preclinical safety assays. Toxicol Sci 134(2):412–426
Huebsch N, Loskill P, Mandegar MA, Marks NC, Sheehan AS, Ma Z, Mathur A, Nguyen TN, Yoo JC, Judge LM, Spencer CI, Chukka AC, Russell CR, So PL, Conklin BR, Healy KE (2014) Automated video-based analysis of contractility and calcium flux in human-induced pluripotent stem cell-derived cardiomyocytes cultured over different spatial scales. Tissue Eng Part C Methods 21(5):467–479
Peters MF, Lamore SD, Guo L, Scott CW, Kolaja KL (2014) Human stem cell-derived cardiomyocytes in cellular impedance assays: bringing cardiotoxicity screening to the front line. Cardiovasc Toxicol 15(2):127–139
Xi B, Wang T, Li N, Ouyang W, Zhang W, Wu J, Xu X, Wang X, Abassi YA (2011) Functional cardiotoxicity profiling and screening using the xCELLigence RTCA cardio system. J Assoc Lab Autom 16(6):415–421
Guo L, Abrams RMC, Babiarz JE, Cohen JD, Kameoka S, Sanders MJ, Chiao E, Kolaja KL (2011) Estimating the risk of drug-induced proarrhythmia using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci 123(1):281–289
Abassi YA, Xi B, Li N, Ouyang W, Seiler A, Watzele M, Kettenhofen R, Bohlen H, Ehlich A, Kolossov E, Wang X, Xu X (2012) Dynamic monitoring of beating periodicity of stem cell-derived cardiomyocytes as a predictive tool for preclinical safety assessment. Br J Pharmacol 165(5):1424–1441
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Science+Business Media LLC
About this protocol
Cite this protocol
Poulton, EJ. (2017). Impedance Measurement in Induced Pluripotent Stem Cell-Derived Cardiomyocytes. In: Gautier, JC. (eds) Drug Safety Evaluation. Methods in Molecular Biology, vol 1641. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7172-5_11
Download citation
DOI: https://doi.org/10.1007/978-1-4939-7172-5_11
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-7170-1
Online ISBN: 978-1-4939-7172-5
eBook Packages: Springer Protocols