Feasibility of using adjunctive optogenetic technologies in cardiomyocyte phenotyping - from the single cell to the whole heart .

We describe how these are overcome by optogenetic tools which put electrically excitable cells under the control of light. We discuss how this enables studies in cardiac material from the single cell to the whole heart scale. We review the current commercial platforms that incorporate optogenetic stimulation strategies, and summarize the global literature to date on cardiac applications of optogenetics. We show that the advantages of optogenetic stimulation relevant to iPS-CM based screening include independence from contact, elimination of electrical stimulation artefacts in field potential measuring approaches such as the multi-electrode array, and the ability to print re-entrant patterns of depolarization at will on 2D cardiomyocyte monolayers. PMID: 30961485 [PubMed - as supplied by publisher]
Source: Current Pharmaceutical Biotechnology - Category: Biotechnology Authors: Tags: Curr Pharm Biotechnol Source Type: research

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This article is protected by copyright. All rights reserved. PMID: 31278749 [PubMed - as supplied by publisher]
Source: The Journal of Physiology - Category: Physiology Authors: Tags: J Physiol Source Type: research
Abstract Tyrosine kinase inhibitors are known to clinically induce various types of cardiovascular adverse events; however, it is still difficult to predict them at preclinical stage. In order to explore how to better predict such drug-induced cardiovascular adverse events, we tried to develop a new protocol by assessing acute electrophysiological, cardiohemodynamic, and cytotoxic effects of dasatinib in vivo and in vitro. Dasatinib at 0.03 and 0.3 mg/kg was intravenously administered to the halothane-anesthetized dogs for 10 min with an interval of 20 min between the dosing (n = 4). M...
Source: Cardiovascular Toxicology - Category: Cardiology Authors: Tags: Cardiovasc Toxicol Source Type: research
Ectopic foci from pulmonary veins (PVs) comprise the main trigger associated with the initiation of atrial fibrillation (AF). An abrupt anatomical narrow-to-wide transition, modeled as in vitro geometrical patterning with similar configuration in the present study, is located at the junction of PVs and the left atrium (LA). Complex cellular composition, i.e., constituent cell heterogeneity, is also observed in PVs and the PV-LA junction. High frequency triggers accompanied with anatomical irregularity and constituent cell heterogeneity provoke impaired conduction, a prerequisite for AF genesis. However, few experiments inv...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Publication date: Available online 21 June 2019Source: Journal of Pharmacological SciencesAuthor(s): Masami Kodama, Kazuharu Furutani, Reiko Kimura, Tomoko Ando, Kazuho Sakamoto, Shushi Nagamori, Takashi Ashihara, Yoshihisa Kurachi, Yuko Sekino, Tetsushi Furukawa, Yasunari Kanda, Junko KurokawaAbstractHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a valuable tool to characterize the pharmacology and toxic effects of drugs on heart cells. In particular, hiPSC-CMs can be used to identify drugs that generate arrhythmias. However, it is unclear whether the expression of genes related to generation o...
Source: Journal of Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research
AbstractHeart failure (HF) is a potentially debilitating condition, with a prognosis comparable to many forms of cancer. It is often complicated by anemia and iron deficiency (ID), which have been shown to even further harm patients ’ functional status and hospitalization risk. Iron is a cellular micronutrient that is essential for oxygen uptake and transportation, as well as mitochondrial energy production. Iron is crucially involved in electrochemical stability, maintenance of structure, and contractility of cardiomyocytes. There is mounting evidence that ID indeed hampers the homeostasis of these properties. Anima...
Source: Heart Failure Reviews - Category: Cardiology Source Type: research
AbstractPurpose of ReviewCardiovascular disease is the leading cause of mortality worldwide. Pluripotent stem cell-derived cardiomyocytes (PSC-CMs) have great potential to treat heart disease, owing to their capacity of engraftment and remuscularization in the host heart after transplantation. In the current review, we provide an overview of PSC-CMs for clinical transplantation.Recent FindingsStudies have shown that PSC-CMs can survive, engraft, and form gap junctions after transplantation, with functional benefit. Engrafted PSC-CMs matured gradually in host hearts. Only in a large animal model, transient ventricular arrhy...
Source: Current Cardiology Reports - Category: Cardiology Source Type: research
Abstract Patient deaths resulting from cardiovascular diseases are increasing across the globe, posing the greatest risk to patients in developed countries. Myocardial infarction, as a result of inadequate blood flow to the myocardium, results in irreversible loss of cardiomyocytes which can lead to heart failure. A sequela of myocardial infarction is scar formation that can alter the normal myocardial architecture and result in arrhythmias. Over the past decade, a myriad of tissue engineering approaches has been developed to fabricate engineered scaffolds for repairing cardiac tissue. This paper highlights the re...
Source: Advanced Drug Delivery Reviews - Category: Drugs & Pharmacology Authors: Tags: Adv Drug Deliv Rev Source Type: research
In this study, the re-entry formation, conduction velocity, and maximum capture rate were investigated in a monolayer of human-induced pluripotent stem cell (iPSC)-derived cardiomyocytes from a healthy donor and in a neonatal rat ventricular myocyte (NRVM) monolayer using the optical mapping method under erythromycin concentrations of 15, 30, and 45 μM. In the monolayer of human iPSC-derived cardiomyocytes, the conduction velocity (CV) varied up to 12 ± 9% at concentrations of 15-45 μM as compared with that of the control, whereas the maximum capture rate (MCR) declined substantially up...
Source: Cardiovascular Toxicology - Category: Cardiology Authors: Tags: Cardiovasc Toxicol Source Type: research
CONCLUSIONS: This proof-of-concept study showed that AAV-mediated delivery of a CaMKII peptide inhibitor to the heart was effective in suppressing arrhythmias in a murine model of CPVT. CaMKII inhibition also reversed the arrhythmia phenotype in human CPVT iPSC-CMs models with different pathogenic mutations. PMID: 31155924 [PubMed - as supplied by publisher]
Source: Circulation - Category: Cardiology Authors: Tags: Circulation Source Type: research
CONCLUSIONS: The results of this exploratory study of intracardiac MSCs administration suggest further research regarding the feasibility and efficacy is warranted. PMID: 31105128 [PubMed - as supplied by publisher]
Source: Circulation Journal - Category: Cardiology Authors: Tags: Circ J Source Type: research
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