scholarly journals The study of the functionality of cardiomyocytes obtained from induced pluripotent stem cells for the modeling of cardiac arrhythmias based on long QT syndrome

2018 ◽  
Vol 22 (2) ◽  
pp. 187-195 ◽  
Author(s):  
M. M. Slotvitsky ◽  
V. A. Tsvelaya ◽  
S. R. Frolova ◽  
E. V. Dement’eva ◽  
K. I. Agladze
Keyword(s):  
Cardiac Tissue ◽  
Single Cells ◽  
Electrophysiological Study ◽  
Heart Rhythm ◽  
Cardiac Cells ◽  
Long Qt ◽  
Induced Pluripotent ◽  
Physiological Values ◽  
Relationship Of ◽  
Lqt Syndrome

There are risk factors that lead the normal conduction of excitation in the heart into a chaotic one. These factors include hereditary and acquired channelopathies. Many dangerous changes in the work of the heart can be identified using the patient’s electrocardiogram. Such relatively easily detectable changes include the long QT interval syndrome (LQTS). Despite a relatively high prevalence of hereditary LQTS, to which it is necessary to add both hereditary and induced LQTS as well as the ease of detection on the ECG, the mechanism of reentry formation in this syndrome is still un­known. What should be noted is a high variability of the hereditary syndrome and the fact of the connection between the increase in the heart rate and the risk of cardiac arrest. After an electrophysiological study on individual cardiac cells from patients with the LQT syndrome, it became apparent that the search for a mechanism for the transition of the normal heart rhythm to chaotic and fibrillation cannot be limited to recording ion currents in single cells. To solve this problem, we need a model of the behavior of cardiac tissue which reflects the relationship of various factors and the risk of reentry. In order to create an experimental model of LQTS in our work, the iPSC of a pati­ent-specific line from a healthy patient was differentiated into a monolayer of cardiac cells and the parameters of the excitation propagation were studied depending on the stage of differentiation. It was shown that a stable value of the propagation velocity and the response to periodic stimulation in the range of physiological values, are reached after the 30th day of dif­ferentiation.

scholarly journals Electrospun Scaffolds and Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Cardiac Tissue Engineering Applications

2020 ◽  
Vol 7 (3) ◽  
pp. 105
Author(s):  
Taylor Cook Suh ◽  
Alaowei Y. Amanah ◽  
Jessica M. Gluck
Keyword(s):  
Tissue Engineering ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Cardiac Tissue ◽  
Complex Structure ◽  
Functional Limitation ◽  
Induced Pluripotent Stem Cell ◽  
Cardiac Cells ◽  
Electrospun Scaffolds ◽  
Induced Pluripotent

Tissue engineering (TE) combines cells, scaffolds, and growth factors to assemble functional tissues for repair or replacement of tissues and organs. Cardiac TE is focused on developing cardiac cells, tissues, and structures—most notably the heart. This review presents the requirements, challenges, and research surrounding electrospun scaffolds and induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) towards applications to TE hearts. Electrospinning is an attractive fabrication method for cardiac TE scaffolds because it produces fibers that demonstrate the optimal potential for mimicking the complex structure of the cardiac extracellular matrix (ECM). iPSCs theoretically offer the capacity to generate limitless numbers of CMs for use in TE hearts, however these iPSC-CMs are electrophysiologically, morphologically, mechanically, and metabolically immature compared to adult CMs. This presents a functional limitation to their use in cardiac TE, and research aiming to address this limitation is presented in this review.

scholarly journals Investigation of the formation of cardiac tissue on substrates of varying degrees of anisotropy and rigidity

2020 ◽  
Vol 49 ◽  
Author(s):  
S. A. Shcherbina ◽  
A. V. Shutko ◽  
A. A. Nizamieva ◽  
A. V. Nikitina ◽  
M. M. Slotvitsky ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cardiac Tissue ◽  
Structural Characteristics ◽  
Embryonic Stem ◽  
Heart Tissue ◽  
Cardiac Cells ◽  
Risk Of Death ◽  
Increased Risk ◽  
Life Threatening ◽  
Induced Pluripotent

In the last decade, in vitro experiments have shown that mechanical properties of the bases could markedly influence the efficacy of differentiation of the induced pluripotent and embryonic stem cells and their development into the mature phenotype. By changing of mechanical, elastic and structural characteristics of the base, it is possible to increase the percentage of stem cells that differentiate to cardiomyocytes.The study was aimed at evaluation of the effects induced by changing physical characteristics of the base on the formation of phenotypic characteristics of cardiac cells. This included the comparison of structural properties of the cultured layer of heart tissue obtained by changing of elasticity and structure of polymeric bases. The results showed significant differences in calcium activity and structural characteristics of cardiomyocytes depending on the base properties, as well as significant variation in the excitation conduction. As long as conduction abnormalities in the heart tissues can often lead to occurrence of life-threatening cardiac arrhythmias, the results can be used to determine patient groups at increased risk of death from heart failure.

scholarly journals Designing a 3D Printing Based Auxetic Cardiac Patch with hiPSC-CMs for Heart Repair

2021 ◽  
Vol 8 (12) ◽  
pp. 172
Author(s):  
Olga Brazhkina ◽  
Jeong Hun Park ◽  
Hyun-Ji Park ◽  
Sruti Bheri ◽  
Joshua T. Maxwell ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
3D Printing ◽  
Cardiac Tissue ◽  
Induced Pluripotent Stem Cell ◽  
Cardiac Cells ◽  
Heart Repair ◽  
Promising Therapeutic Approach ◽  
Tunable Mechanical Properties ◽  
Induced Pluripotent ◽  
Cardiac Patch

Myocardial infarction is one of the largest contributors to cardiovascular disease and reduces the ability of the heart to pump blood. One promising therapeutic approach to address the diminished function is the use of cardiac patches composed of biomaterial substrates and cardiac cells. These patches can be enhanced with the application of an auxetic design, which has a negative Poisson’s ratio and can be modified to suit the mechanics of the infarct and surrounding cardiac tissue. Here, we examined multiple auxetic models (orthogonal missing rib and re-entrant honeycomb in two orientations) with tunable mechanical properties as a cardiac patch substrate. Further, we demonstrated that 3D printing based auxetic cardiac patches of varying thicknesses (0.2, 0.4, and 0.6 mm) composed of polycaprolactone and gelatin methacrylate can support induced pluripotent stem cell-derived cardiomyocyte function for 14-day culture. Taken together, this work shows the potential of cellularized auxetic cardiac patches as a suitable tissue engineering approach to treating cardiovascular disease.

scholarly journals Doxorubicin induces caspase-mediated proteolysis of KV7.1

2018 ◽  
Author(s):  
Anne Strigli ◽  
Christian Raab ◽  
Sabine Hessler ◽  
Tobias Huth ◽  
Adam J. T. Schuldt ◽  
...  
Keyword(s):  
Posttranslational Modification ◽  
Potassium Current ◽  
Induced Pluripotent Stem Cell ◽  
Neonatal Rat ◽  
Loss Of Function ◽  
Long Qt ◽  
Human Cardiomyocytes ◽  
Induced Pluripotent ◽  
Lqt Syndrome ◽  
Cardiac Potassium Current

AbstractThe voltage-gated potassium channel Kv7.1 (KCNQ1) co-assembles with KCNE1 to generate the cardiac potassium current IKs. Gain- and loss-of-function mutations in KCNQ1 are associated with atrial fibrillation and long-QT (LQT) syndrome, respectively, highlighting the importance of modulating IKS activity for proper cardiac function. On a post-translational level, IKS can be regulated by phosphorylation, ubiquitination and sumoylation. Here, we report proteolysis of Kv7.1 as a novel, irreversible posttranslational modification. The identification of two C-terminal fragments (CTF1 and CTF2) of Kv7.1 led us to identify an aspartate critical for the generation of CTF2 and caspases as responsible for mediating Kv7.1 proteolysis. Activating caspases by apoptotic stimuli significantly reduced Kv7.1/KCNE1 currents, which was abrogated in cells expressing caspase-resistant Kv7.1 D459A/KCNE1 channels. An increase in cleavage of Kv7.1 could be detected in the case of LQT mutation G460S, which is located adjacent to the cleavage site. Application of apoptotic stimuli or doxorubicin-induced cardiotoxicity provoked caspase-mediated cleavage of endogenous Kv7.1 in human cardiomyocytes. In summary, our findings establish caspases as novel regulatory components for modulating Kv7.1 activity which may have important implications for the molecular mechanism of doxorubicin-induced cardiotoxicity.Non-standard Abbreviations and AcronymsCamcalmodulinEBCequilibrium buffer contentLQT syndromelong QT syndromeNRVMNeonatal rat ventricular cardiomyocyteshiPSC-CMshuman induced pluripotent stem cell-derived cardiomyocytes

scholarly journals Optical Recording of Action Potentials in Human Induced Pluripotent Stem Cell-Derived Cardiac Single Cells and Monolayers Generated from Long QT Syndrome Type 1 Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Tadashi Takaki ◽  
Azusa Inagaki ◽  
Kazuhisa Chonabayashi ◽  
Keiji Inoue ◽  
Kenji Miki ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Single Cell ◽  
High Throughput ◽  
Action Potentials ◽  
Single Cells ◽  
Optical Recording ◽  
Long Qt ◽  
Ventricular Cells ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPSCs) from type 1 long QT (LQT1) patients can differentiate into cardiomyocytes (CMs) including ventricular cells to recapitulate the disease phenotype. Although optical recordings using membrane potential dyes to monitor action potentials (APs) were reported, no study has investigated the disease phenotypes of cardiac channelopathy in association with the cardiac subtype at the single-cell level. We induced iPSC-CMs from three control and three LQT1 patients. Single-cell analysis using a fast-responding dye confirmed that ventricular cells were the dominant subtype (control-iPSC-CMs: 98%, 88%, 91%; LQT1-iPSC-CMs: 95%, 79%, 92%). In addition, LQT1-iPSC-ventricular cells displayed an increased frequency of early afterdepolarizations (pvalue=0.031). Cardiomyocyte monolayers constituted mostly of ventricular cells derived from LQT1-iPSCs showed prolonged AP duration (APD) (pvalue=0.000096). High-throughput assays using cardiomyocyte monolayers in 96-well plates demonstrated that IKr inhibitors prolonged APDs in both control- and LQT1-iPSC-CM monolayers. We confirmed that the optical recordings of APs in single cells and monolayers derived from control- and LQT1-iPSC-CMs can be used to assess arrhythmogenicity, supporting the feasibility of membrane potential dye-based high-throughput screening to study ventricular arrhythmias caused by genetic channelopathy or cardiotoxic drugs.

Confocal imaging of calcium in intact ventricular muscle provides a new view of excitation-contraction coupling

1996 ◽  
Vol 54 ◽  
pp. 738-739
Author(s):  
W.G. Wier
Keyword(s):  
Local Control ◽  
Cardiac Tissue ◽  
Cell Function ◽  
Isolated Heart ◽  
Cardiac Cells ◽  
Confocal Imaging ◽  
Ion Concentration ◽  
Heart Cell ◽  
Free Calcium ◽  
Heart Cells

A fundamentally new understanding of cardiac excitation-contraction (E-C) coupling is being developed from recent experimental work using confocal microscopy of single isolated heart cells. In particular, the transient change in intracellular free calcium ion concentration ([Ca2+]i transient) that activates muscle contraction is now viewed as resulting from the spatial and temporal summation of small (∼ 8 μm3), subcellular, stereotyped ‘local [Ca2+]i-transients' or, as they have been called, ‘calcium sparks'. This new understanding may be called ‘local control of E-C coupling'. The relevance to normal heart cell function of ‘local control, theory and the recent confocal data on spontaneous Ca2+ ‘sparks', and on electrically evoked local [Ca2+]i-transients has been unknown however, because the previous studies were all conducted on slack, internally perfused, single, enzymatically dissociated cardiac cells, at room temperature, usually with Cs+ replacing K+, and often in the presence of Ca2-channel blockers. The present work was undertaken to establish whether or not the concepts derived from these studies are in fact relevant to normal cardiac tissue under physiological conditions, by attempting to record local [Ca2+]i-transients, sparks (and Ca2+ waves) in intact, multi-cellular cardiac tissue.

scholarly journals Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 563
Author(s):  
Magali Seguret ◽  
Eva Vermersch ◽  
Charlène Jouve ◽  
Jean-Sébastien Hulot
Keyword(s):  
Tissue Engineering ◽  
Drug Testing ◽  
Cardiac Tissue ◽  
Cardiac Tissue Engineering ◽  
Cardiac Cells ◽  
Cardiac Functions ◽  
Different Types ◽  
Recent Developments ◽  
Human Cardiac Tissue ◽  
Key Aspects

Cardiac tissue engineering aims at creating contractile structures that can optimally reproduce the features of human cardiac tissue. These constructs are becoming valuable tools to model some of the cardiac functions, to set preclinical platforms for drug testing, or to alternatively be used as therapies for cardiac repair approaches. Most of the recent developments in cardiac tissue engineering have been made possible by important advances regarding the efficient generation of cardiac cells from pluripotent stem cells and the use of novel biomaterials and microfabrication methods. Different combinations of cells, biomaterials, scaffolds, and geometries are however possible, which results in different types of structures with gradual complexities and abilities to mimic the native cardiac tissue. Here, we intend to cover key aspects of tissue engineering applied to cardiology and the consequent development of cardiac organoids. This review presents various facets of the construction of human cardiac 3D constructs, from the choice of the components to their patterning, the final geometry of generated tissues, and the subsequent readouts and applications to model and treat cardiac diseases.

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