Human iPSC models of cardiac electrophysiology and arrhythmia

2022 ◽  
pp. 29-93
Author(s):  
Brenda Yang ◽  
Justin Lowenthal ◽  
Gordon F. Tomaselli ◽  
Leslie Tung
Keyword(s):  
Cardiac Electrophysiology ◽  
Human Ipsc

scholarly journals Contribution of two-pore K+ channels to cardiac ventricular action potential revealed using human iPSC-derived cardiomyocytes

2017 ◽  
Vol 312 (6) ◽  
pp. H1144-H1153 ◽  
Author(s):  
Sam Chai ◽  
Xiaoping Wan ◽  
Drew M. Nassal ◽  
Haiyan Liu ◽  
Christine S. Moravec ◽  
...  
Keyword(s):  
Action Potential ◽  
Expression Profile ◽  
Cardiac Electrophysiology ◽  
Human Heart ◽  
Induced Pluripotent Stem Cell ◽  
Heart Tissue ◽  
Induced Pluripotent ◽  
Interfering Rna ◽  
Human Ipsc ◽  
Physiological Systems

Two-pore K+ (K2p) channels have been described in modulating background conductance as leak channels in different physiological systems. In the heart, the expression of K2p channels is heterogeneous with equivocation regarding their functional role. Our objective was to determine the K2p expression profile and their physiological and pathophysiological contribution to cardiac electrophysiology. Induced pluripotent stem cells (iPSCs) generated from humans were differentiated into cardiomyocytes (iPSC-CMs). mRNA was isolated from these cells, commercial iPSC-CM (iCells), control human heart ventricular tissue (cHVT), and ischemic (iHF) and nonischemic heart failure tissues (niHF). We detected 10 K2p channels in the heart. Comparing quantitative PCR expression of K2p channels between human heart tissue and iPSC-CMs revealed K2p1.1, K2p2.1, K2p5.1, and K2p17.1 to be higher expressed in cHVT, whereas K2p3.1 and K2p13.1 were higher in iPSC-CMs. Notably, K2p17.1 was significantly lower in niHF tissues compared with cHVT. Action potential recordings in iCells after K2p small interfering RNA knockdown revealed prolongations in action potential depolarization at 90% repolarization for K2p2.1, K2p3.1, K2p6.1, and K2p17.1. Here, we report the expression level of 10 human K2p channels in iPSC-CMs and how they compared with cHVT. Importantly, our functional electrophysiological data in human iPSC-CMs revealed a prominent role in cardiac ventricular repolarization for four of these channels. Finally, we also identified K2p17.1 as significantly reduced in niHF tissues and K2p4.1 as reduced in niHF compared with iHF. Thus, we advance the notion that K2p channels are emerging as novel players in cardiac ventricular electrophysiology that could also be remodeled in cardiac pathology and therefore contribute to arrhythmias. NEW & NOTEWORTHY Two-pore K+ (K2p) channels are traditionally regarded as merely background leak channels in myriad physiological systems. Here, we describe the expression profile of K2p channels in human-induced pluripotent stem cell-derived cardiomyocytes and outline a salient role in cardiac repolarization and pathology for multiple K2p channels.

Human iPSC-derived cardiomyocytes (iCell™) and DrugPrint®: A suitable assay platform for cardiac electrophysiology

2011 ◽  
Vol 64 (1) ◽  
pp. e16
Author(s):  
Simon Bryant ◽  
Chris Wylie ◽  
Rebecca Palmer ◽  
Steve Fiene ◽  
Blake D. Anson ◽  
...  
Keyword(s):  
Cardiac Electrophysiology ◽  
Human Ipsc

High-Frequency Cardiac Electrophysiology

2019 ◽  
Author(s):  
Pavel Jurak ◽  
Josef Halamek ◽  
Pavel Leinveber ◽  
Filip Plesinger ◽  
Ivo Viscor ◽  
...  
Keyword(s):  
High Frequency ◽  
Cardiac Electrophysiology

Subclinical Thyroid Dysfunction and the Risk of Cardiovascular Disease

2020 ◽  
Vol 26 (43) ◽  
pp. 5617-5627
Author(s):  
Mirjana Stojković ◽  
Miloš Žarković
Keyword(s):  
Cardiovascular Disease ◽  
Risk Factor ◽  
Cardiac Electrophysiology ◽  
Vascular System ◽  
Density Lipoprotein ◽  
Thyroid Stimulating Hormone ◽  
Normal Limits ◽  
Developing Heart ◽  
Treatment Indications ◽  
Increased Risk

The prevalence of subclinical hypothyroidism (SH) is 3-10%. The prevalence of subclinical hyperthyroidism (SHr) is 0.7-9.7%. Thyroid hormones affect cardiac electrophysiology, contractility, and vasculature. SH is associated with an increased risk of coronary heart disease (CHD), especially in subjects under 65. SHr seems to be associated with a slightly increased risk of CHD and an increase in CHD-related mortality. Both SH and SHr carry an increased risk of developing heart failure (HF), especially in those under 65. Both SH and SHr are associated with worse prognoses in patients with existing HF. SH is probably not associated with atrial fibrillation (AF). SHr, low normal thyroid-stimulating hormone (TSH) and high normal free thyroxine (FT4) are all associated with the increased risk of AF. An association between endothelial dysfunction and SH seems to exist. Data regarding the influence of SHr on the peripheral vascular system are conflicting. SH is a risk factor for stroke in subjects under 65. SHr does not increase the risk of stroke. Both SH and SHr have an unfavourable effect on cardiovascular disease (CVD) and all-cause mortality. There is a U-shaped curve of mortality in relation to TSH concentrations. A major factor that modifies the relation between subclinical thyroid disease (SCTD) and mortality is age. SH increases blood pressure (BP). SHr has no significant effect on BP. Lipids are increased in patients with SH. In SHr, high-density lipoprotein cholesterol and lipoprotein( a) are increased. SCTD should be treated when TSH is over 10 mU/l or under 0.1 mU/l. Treatment indications are less clear when TSH is between normal limits and 0.1 or 10 mU/L. The current state of knowledge supports the understanding of SCTD’s role as a risk factor for CVD development. Age is a significant confounding factor, probably due to age-associated changes in the TSH reference levels.

scholarly journals Machine-readable Yin–Yang imbalance: traditional Chinese medicine syndrome computer modeling based on three-dimensional noninvasive cardiac electrophysiology imaging

2019 ◽  
Vol 47 (4) ◽  
pp. 1580-1591 ◽  
Author(s):  
Wei Cen ◽  
Ralph Hoppe ◽  
Aiwu Sun ◽  
Hongyan Ding ◽  
Ning Gu
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Electrical Activity ◽  
Computer Modeling ◽  
Cardiac Electrophysiology ◽  
Three Dimensional ◽  
Mathematical Physics ◽  
Syndrome Differentiation ◽  
Physics Model ◽  
Machine Readable

Objectives The principal diagnostic methods of traditional Chinese medicine (TCM) are inspection, auscultation and olfaction, inquiry, and pulse-taking. Treatment by syndrome differentiation is likely to be subjective. This study was designed to provide a basic theory for TCM diagnosis and establish an objective means of evaluating the correctness of syndrome differentiation. Methods We herein provide the basic theory of TCM syndrome computer modeling based on a noninvasive cardiac electrophysiology imaging technique. Noninvasive cardiac electrophysiology imaging records the heart’s electrical activity from hundreds of electrodes on the patient’s torso surface and therefore provides much more information than 12-lead electrocardiography. Through mathematical reconstruction algorithm calculations, the reconstructed heart model is a machine-readable description of the underlying mathematical physics model that reveals the detailed three-dimensional (3D) electrophysiological activity of the heart. Results From part of the simulation results, the imaged 3D cardiac electrical source provides dynamic information regarding the heart’s electrical activity at any given location within the 3D myocardium. Conclusions This noninvasive cardiac electrophysiology imaging method is suitable for translating TCM syndromes into a computable format of the underlying mathematical physics model to offer TCM diagnosis evidence-based standards for ensuring correct evaluation and rigorous, scientific data for demonstrating its efficacy.

scholarly journals Rapid 3D BioPrinting of a human iPSC-derived cardiac micro-tissue for high-throughput drug testing

2021 ◽  
Vol 3 ◽  
pp. 100007
Author(s):  
Kathleen L. Miller ◽  
Yi Xiang ◽  
Claire Yu ◽  
Jacob Pustelnik ◽  
Jerry Wu ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Testing ◽  
3D Bioprinting ◽  
Human Ipsc

scholarly journals An Efficient Method for the Differentiation of Human iPSC-Derived Endoderm toward Enterocytes and Hepatocytes

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 812
Author(s):  
Shimeng Qiu ◽  
Yaling Li ◽  
Yuki Imakura ◽  
Shinji Mima ◽  
Tadahiro Hashita ◽  
...  
Keyword(s):  
Small Intestine ◽  
Activin A ◽  
Double Positive ◽  
Differentiation Method ◽  
Drug Metabolizing Enzyme ◽  
Human Ipscs ◽  
Novel Method ◽  
Induced Pluripotent ◽  
Metabolizing Enzyme ◽  
Human Ipsc

The endoderm, differentiated from human induced pluripotent stem cells (iPSCs), can differentiate into the small intestine and liver, which are vital for drug absorption and metabolism. The development of human iPSC-derived enterocytes (HiEnts) and hepatocytes (HiHeps) has been reported. However, pharmacokinetic function-deficiency of these cells remains to be elucidated. Here, we aimed to develop an efficient differentiation method to induce endoderm formation from human iPSCs. Cells treated with activin A for 168 h expressed higher levels of endodermal genes than those treated for 72 h. Using activin A (days 0–7), CHIR99021 and PI−103 (days 0–2), and FGF2 (days 3–7), the hiPSC-derived endoderm (HiEnd) showed 97.97% CD−117 and CD−184 double-positive cells. Moreover, HiEnts derived from the human iPSC line Windy had similar or higher expression of small intestine-specific genes than adult human small intestine. Activities of the drug transporter P-glycoprotein and drug-metabolizing enzyme cytochrome P450 (CYP) 3A4/5 were confirmed. Additionally, Windy-derived HiHeps expressed higher levels of hepatocyte- and pharmacokinetics-related genes and proteins and showed higher CYP3A4/5 activity than those derived through the conventional differentiation method. Thus, using this novel method, the differentiated HiEnts and HiHeps with pharmacokinetic functions could be used for drug development.

Sign in / Sign up

Export Citation Format

Share Document