scholarly journals The influence of light on the beat rate variability of murine embryonic stem cell derived cardiomyocytes

2022 ◽  
Vol 146 ◽  
pp. 112589
Author(s):  
Julius Niehoff ◽  
Matthias Matzkies ◽  
Filomain Nguemo ◽  
Jürgen Hescheler ◽  
Michael Reppel
2016 ◽  
Vol 38 (2) ◽  
pp. 646-658 ◽  
Author(s):  
Julius Niehoff ◽  
Matthias Matzkies ◽  
Filomain Nguemo ◽  
Jürgen Hescheler ◽  
Michael Reppel

Background/Aims: Heart rate variability (HRV) refers to the fluctuation of the time interval between consecutive heartbeats in humans. It has recently been discovered that cardiomyocytes derived from human embryonic and induced pluripotent stem cells show beat rate variability (BRV) that is similar to the HRV in humans. In the present study, clinical aspects of HRV were transferred to an in vitro model. The aims of the study were to explore the BRV in murine embryonic stem cell (mESC)-derived cardiomyocytes and to demonstrate the influence of antiarrhythmic drugs on BRV as has been shown in clinical trials previously. Methods: The Microelectrode Array (MEA) technique was used to perform short-term recordings of extracellular field potentials (FPs) of spontaneously beating cardiomyocytes derived from mESCs (D3 cell line, αPig-44). Offline analysis was focused on time domain and nonlinear methods. Results: The Poincaré-Plot analysis of measurements without pharmacological intervention revealed that three different shapes of scatter plots occurred most frequently. Comparable shapes have been described in clinical studies before. The antiarrhythmic drugs Ivabradine, Verapamil and Sotalol augmented BRV, whereas Flecainide decreased BRV parameters at low concentrations (SDSD 79.0 ± 8.7% of control at 10-9 M, p < 0.05) and increased variability measures at higher concentrations (SDNN 258.8 ± 42.7% of control at 10-5 M, p < 0.05). Amiodarone and Metoprolol did not alter BRV significantly. Conclusions: Spontaneously beating cardiomyocytes derived from mESCs showed BRV that appears to be similar to the HRV known from humans. Antiarrhythmic drugs affected BRV parameters similar to clinical observations. Therefore, our study demonstrates that this in vitro model can contribute to a better understanding of electrophysiological properties of mESC-derived cardiomyocytes and might serve as a valuable tool for drug safety screening.


Amino Acids ◽  
2013 ◽  
Vol 45 (6) ◽  
pp. 1343-1351 ◽  
Author(s):  
Miho Tamai ◽  
Mami Aoki ◽  
Akihito Nishimura ◽  
Koji Morishita ◽  
Yoh-ichi Tagawa

2007 ◽  
Vol 8 (9) ◽  
pp. R184 ◽  
Author(s):  
Michael Doss ◽  
Shuhua Chen ◽  
Johannes Winkler ◽  
Rita Hippler-Altenburg ◽  
Margareta Odenthal ◽  
...  

2010 ◽  
Vol 15 (3) ◽  
pp. 209-228 ◽  
Author(s):  
Michael Xavier Doss ◽  
Vilas Wagh ◽  
Herbert Schulz ◽  
Meelis Kull ◽  
Raivo Kolde ◽  
...  

2009 ◽  
Vol 75A (2) ◽  
pp. 121-129 ◽  
Author(s):  
Hamed Shadpour ◽  
Christopher E. Sims ◽  
Randy J. Thresher ◽  
Nancy L. Allbritton

2012 ◽  
Vol 17 (5) ◽  
pp. 683-691 ◽  
Author(s):  
Tadahiro Shinozawa ◽  
Hatsue Furukawa ◽  
Eimei Sato ◽  
Kenji Takami

Cardiomyocytes derived from embryonic stem cells (ES-CMs) and induced pluripotent stem cells (iPS-CMs) are useful for toxicity and pharmacology screening. In the present study, we found that cardiomyocyte-rich beating cell clusters (CCs) emerged from murine embryonic stem cell (mESC)–derived beating EBs and from human-induced pluripotent stem cell (hiPSC)–derived beating EBs dissociated by gentle pipetting with a thin glass pipette. The percentage of cardiac troponin T (cTnT)–positive cells in the beating CCs obtained from mESC-derived and hiPSC-derived beating EBs was higher (81.5% and 91.6%, respectively) than in beating-undissociated EBs (13.7% and 67.1%, respectively). For mESCs, the yield of cTnT-positive cells from beating CCs was estimated to be 1.6 times higher than that of beating EBs. The bromodeoxyuridine labeling index of mouse ES-CMs and human iPS-CMs in beating CCs was 1.5- and 3.2-fold, respectively, greater than those in beating EBs. To investigate the utility of the cells in toxicity assessment, we showed that doxorubicin, a cardiotoxic drug, induced myofilament disruption in cardiomyocytes isolated by this method. This simple method enables preparation of mouse ES-CMs and human iPS-CMs with better proliferative activity than beating EBs not dissociated by pipetting, and the cardiomyocytes are useful for drug-induced myocardial toxicity testing.


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