QTempo assay service

Product Classification : Human iPS Cells Derived CardiomyocytesResearch Theme : Safety Test, Toxicology test

QTempo assay service

Cardiotoxicity Assay Services Using Human iPSC Derived Beating Cardiomyocytes

  • QT prolongation assay service using human cardiomyocytes derived from iPS cells
  • ECG-like recordings by using extracellular electrodes
  • Results in excellent agreement with clinical findings
  • Ideal as Post HTS/Hit-to-Lead non-GLP test
  • Covers all cardiac ion channels including hERG channel
  • Screens non-ion channel factors as well
  • Also for beat rate change detection

QTempo is a pre-clinical functional assay that captures the whole complexity of cardiac activity in vitro. By making ECG-like recordings composed of QRS complex and T wave, QTempo can capture the critical cardiac parameters including QT interval and beat rate.

The cardiomyocyte clusters used in QTempo generate robust, consistent data over extended periods. This allows a wide variety of drug concentrations to be sequentially tested, increasing confidence in drug safety before further development. QTempo has generated results in complete agreement with clinical findings, even with cardiotoxic compounds not identified by hERG assay.

Overview

Strict quality control of QTempo assay service

The cardiomyocyte clusters used in our assay service are strictly quality-checked before use.

  • Amplitude of Na+ amplitude: 40 uV or larger
  • Amplitude of K+ amplitude: 2 uV or larger
  • Interval between K+-wave and Na+-wave: < 600 msec
  • Beat rate: 30~60 beats/minute
    (average of 3 minute measurement of untreated cells)
  • Variation of beat rate: < 10 bpm

Data

Test results of QTempo, ReproCELL's cardiotoxicity assay using ReproCardio cardiomyocytes

Data obtained by QTempo assay

With QTempo assay, safety pharmacology studies with?in vivo?ECG-like recordings are possible?in vitro. The figures below show the QT prolongation analysis with?Astemizole, a potent histamine H1-receptor antagonist withdrawn from market due to QT prolongation. QTempo also allows the quantification of other parameters including beat rate and the effects on numerous kinds of ion channels, not just K+ channels, at the same time.

*Click the figure to enlarge

Comparison of QTempo and hERG assay

Figure 1 is the comparison of the test results for 8 compounds from QTempo and the published hERG assay reports. In terms of detection of the QT prolongation, QTempo replicated the?in vivo?results better than hERG assay, the current standard?in vitro?assay (see the highlighted rows for dl-Sotalol and Verapamil).

*Click the figure to enlarge

Figure 1: Comparison between QTempo & hERG assay for detection of cardiotoxicity

QTempo can be conducted using ReproCardio (human iPSC-cardiomyocytes), human ESC-cardiomyocytes and monkey ESC-cardiomyocytes.

Presentations

  • Society for Biomolecular Sciences(SBS), 14th AnnualConference & Exhibition 2008 (St. Louis), poster session, April 2008.
  • IBC Asia's 4th Annual Stem Cells Asia Congress (Singapore), oral session, June 2008.
  • ELRIG and SBS Present: Drug Discovery (UK) poster session, September 2008.
  • Advances in Stem Cell Discoveries (San Francisco) oral session, September 2008.
  • Stem Cells: Drug Discovery and Therapeutics (London) oral session, February 2008.
  • Society for Biomolecular Science 15th Annual Conference (France), poster session, Best Poster 2009 Award-winning, April 2009.
  • Stem Cells and Regenerative Medicine Europe (UK), September 2009, Best Poster 2009 Award-winning.
  • MipTec Conference 2009, October 13-15, Basel Invited Lecture.
  • The 74th Annual Scientific Meeting of the Japanese Circulation Society (Kyoto), March 2010.
  • The 130th The Pharmaceutical Society of Japan (Okayama), March 2010.
  • The Society of Toxicology (SOT) 51st Annual Meeting (CA, USA), poster session, March 2012.
  • Safety Pharmacology Society (SPS), 13th annual meeting 2013 (Rotterdam, Netherlands), poster session, September 2013.
  • Automated Patch-Clamp systems and Ion Channel Expressing Cells 2013 (Tokyo), Verbal presentation 2013 Nov.
  • The 7th Takeda Science Foundation Symposium (Osaka), Poster presentation 2014 Jan.

References

ReproCardio, ReproCardio2

  • Datta-Chaudhuri, Timir, Pamela Abshire, and Elisabeth Smela. "Packaging commercial CMOS chips for lab on a chip integration." Lab on a chip 14.10 (2014): 1753-1766.
  • Datta-Chaudhuri, Timir, Pamela Abshire, and Elisabeth Smela. "Packaging commercial CMOS chips for lab on a chip integration." Lab on a chip 14.10 (2014): 1753-1766.
  • Mandenius, Carl-Fredrik, and Thomas Meyer. "High-throughput screening assays to evaluate the cardiotoxic potential of drugs." High-Throughput Screening Methods in Toxicity Testing (2013): 403-420.
  • Scott, Clay W., Matthew F. Peters, and Yvonne P. Dragan. "Human induced pluripotent stem cells and their use in drug discovery for toxicity testing." Toxicology letters 219.1 (2013): 49-58.
  • Takeuchi, Akimasa, et al. "Microfabricated device for co-culture of sympathetic neuron and iPS-derived cardiomyocytes." Engineering in Medicine and Biology Society (EMBC), 2013 35th Annual International Conference of the IEEE. IEEE, 2013.
  • Asai, Yasuyuki, et al. "Combination of functional cardiomyocytes derived from human stem cells and a highly-efficient microelectrode array system: an ideal hybrid model assay for drug development." Current stem cell research & therapy 5.3 (2010): 227-232.
  • Asai, Y. "Direct measurement of the QT interval in stem cell-derived cardiomyocytes for the assessment of QT liability." Nihon yakurigaku zasshi. Folia pharmacologica Japonica 134.6 (2009): 320-324.
  • Szebenyi, Kornelia, et al. "Human pluripotent stem cells in pharmacological and toxicological screening: new perspectives for personalized medicine." Personalized Medicine 8.3 (2011): 347-364.

QTempo assay

  • Vidarsson, Hilmar, Johan Hyllner, and Peter Sartipy. "Differentiation of human embryonic stem cells to cardiomyocytes for in vitro and in vivo applications."Stem Cell Reviews and Reports 6.1 (2010): 108-120.
  • Lecina, Marti, et al. "Scalable platform for human embryonic stem cell differentiation to cardiomyocytes in suspended microcarrier cultures." Tissue Engineering Part C: Methods 16.6 (2010): 1609-1619.
  • Phillips, Blaine W., and Jeremy M. Crook. "Pluripotent Human Stem Cells."BioDrugs 24.2 (2010): 99-108.

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