scholarly journals Beat Rate Variability in Murine Embryonic Stem Cell-Derived Cardiomyocytes: Effect of Antiarrhythmic Drugs

2016 ◽  
Vol 38 (2) ◽  
pp. 646-658 ◽  
Author(s):  
Julius Niehoff ◽  
Matthias Matzkies ◽  
Filomain Nguemo ◽  
Jürgen Hescheler ◽  
Michael Reppel
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Antiarrhythmic Drugs ◽  
In Vitro Model ◽  
Embryonic Stem ◽  
Pharmacological Intervention ◽  
Murine Embryonic Stem Cell ◽  
Beat Rate ◽  
Vitro Model

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.

scholarly journals Human Embryonic Stem Cell-Derived Epithelial Cells in a Novel In Vitro Model of Vocal Mucosa

2013 ◽  
Vol 19 (19-20) ◽  
pp. 2233-2241 ◽  
Author(s):  
Ciara Leydon ◽  
Joshua A. Selekman ◽  
Sean Palecek ◽  
Susan L. Thibeault
Keyword(s):  
Stem Cell ◽  
Epithelial Cells ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
In Vitro Model ◽  
Embryonic Stem ◽  
Vitro Model

scholarly journals Engraftment of human embryonic stem cell derived cardiomyocytes improves conduction in an arrhythmogenic in vitro model

2012 ◽  
Vol 53 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Susan A. Thompson ◽  
Paul W. Burridge ◽  
Elizabeth A. Lipke ◽  
Michael Shamblott ◽  
Elias T. Zambidis ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
In Vitro Model ◽  
Embryonic Stem ◽  
Vitro Model

scholarly journals Aggregate Culture of Human Embryonic Stem Cell-Derived Hepatocytes in Suspension Are an Improved In Vitro Model for Drug Metabolism and Toxicity Testing

2014 ◽  
Vol 140 (1) ◽  
pp. 236-245 ◽  
Author(s):  
Srikumar Sengupta ◽  
Brian Patrick Johnson ◽  
Scott Allen Swanson ◽  
Ron Stewart ◽  
Christopher Alan Bradfield ◽  
...  
Keyword(s):  
Stem Cell ◽  
Drug Metabolism ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
In Vitro Model ◽  
Embryonic Stem ◽  
Toxicity Testing ◽  
Aggregate Culture ◽  
Vitro Model

scholarly journals The Effect of Antiarrhythmic Drugs on the Beat Rate Variability of Human Embryonic and Human Induced Pluripotent Stem Cell Derived Cardiomyocytes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Julius Niehoff ◽  
Matthias Matzkies ◽  
Filomain Nguemo ◽  
Jürgen Hescheler ◽  
Michael Reppel
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Antiarrhythmic Drugs ◽  
Embryonic Stem ◽  
Induced Pluripotent Stem Cell ◽  
Pharmacological Intervention ◽  
Beat Rate ◽  
Induced Pluripotent

Abstract Embryonic stem cell (ESC) derived tissue is a promising tool to be used in different clinical, preclinical and also scientific settings, for example as in vivo biological pacemaker, preclinical drug safety screening tool or ultimately as part of a cell replacement therapy. However, before ESC derived tissue can be used routinely for these purposes in humans, further studies are needed. In this context, the aims of the present study were to examine the effect of antiarrhythmic drugs on human ESC (hESC) und human induced pluripotent stem cell (hiPSC) derived cardiomyocytes by analyzing the beat rate variability (BRV), which can be considered as the in vitro equivalent of the heart rate variability (HRV) in vivo. Short-term recordings of extracellular field potentials of spontaneously beating cardiomyocytes derived from hESCs and hiPSCs were made using Microelectrode Arrays (MEA). The effect of Flecainide, Ivabradine and Metoprolol was tested. The offline analysis of the BRV was mainly focused on time domain methods. Additionally a non-linear analysis method was used. The evaluation of the Poincaré-Plots of the measurements without pharmacological intervention revealed that the vast majority of the scatter plots have a similar, ellipsoid shape. Flecainide and Ivabradine influenced BRV parameters significantly, whereas Metoprolol did not alter the BRV markedly. We detected remarkable similarities between the BRV of hESC and hiPSC derived cardiomyocytes in vitro and the HRV in vivo. The effect of antiarrhythmic drugs on spontaneously beating cardiomyocytes derived from hESC and hiPSC was generally consistent with clinical experiences and also with our previous study based on murine ESC derived cardiomyocytes. In conclusion, our study points out the great potential of hESC and hiPSC derived tissue to be used routinely for many different applications in medicine and science.

scholarly journals A novel in vitro model system for smooth muscle differentiation from human embryonic stem cell-derived mesenchymal cells

2013 ◽  
Vol 304 (4) ◽  
pp. C289-C298 ◽  
Author(s):  
Xia Guo ◽  
Steven L. Stice ◽  
Nolan L. Boyd ◽  
Shi-You Chen
Keyword(s):  
Smooth Muscle ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
In Vitro Model ◽  
Embryonic Stem ◽  
Mesenchymal Cells ◽  
Dependent Manner ◽  
Vitro Model

The objective of this study was to develop a novel in vitro model for smooth muscle cell (SMC) differentiation from human embryonic stem cell-derived mesenchymal cells (hES-MCs). We found that hES-MCs were differentiated to SMCs by transforming growth factor-β (TGF-β) in a dose- and time-dependent manner as demonstrated by the expression of SMC-specific genes smooth muscle α-actin, calponin, and smooth muscle myosin heavy chain. Under normal growth conditions, however, the differentiation capacity of hES-MCs was very limited. hES-MC-derived SMCs had an elongated and spindle-shaped morphology and contracted in response to the induction of carbachol and KCl. KCl-induced calcium transient was also evident in these cells. Compared with the parental cells, TGF-β-treated hES-MCs sustained the endothelial tube formation for a longer time due to the sustained SMC phenotype. Mechanistically, TGF-β-induced differentiation was both Smad- and serum response factor/myocardin dependent. TGF-β regulated myocardin expression via multiple signaling pathways including Smad2/3, p38 MAPK, and PI3K. Importantly, we found that a low level of myocardin was present in mesoderm prior to SMC lineage determination, and a high level of myocardin was not induced until the differentiation process was initiated. Taken together, our study characterized a novel SMC differentiation model that can be used for studying human SMC differentiation from mesoderm during vascular development.

scholarly journals Human embryonic stem cell-derived cardiomyocytes as an in vitro model to study cardiac insulin resistance

2018 ◽  
Vol 1864 (5) ◽  
pp. 1960-1967 ◽  
Author(s):  
Ilvy M.E. Geraets ◽  
Dipanjan Chanda ◽  
Florence H.J. van Tienen ◽  
Arthur van den Wijngaard ◽  
Rick Kamps ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
In Vitro Model ◽  
Embryonic Stem ◽  
Vitro Model
Sign in / Sign up

Export Citation Format

Share Document