Ascorbic Acid-Induced Cardiac Differentiation of Murine Pluripotent Stem Cells: Transcriptional Profiling and Effect of a Small Molecule Synergist of Wnt/β-Catenin Signaling Pathway

Ivanyuk, Dina; Budash, Galyna; Zheng, Yongqiang; Gaspar, John Antonydas; Chaudhari, Umesh; Fatima, Azra; Bahmanpour, Soghra; Grin, Vladislav K; Попандопуло, А. Г.; Sachinidis, Agapios; Hescheler, Jürgen; Šarić, Tomo

doi:10.1159/000430140

Cited by 26 publications

(24 citation statements)

References 49 publications

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“…Hence, the findings of this study support the hypothesis that iPS-derived cardiac myocytes can provide an adequate model for pharmacological and toxicological studies. New strategies for the differentiation of stem cells promise to improve the functional consistency of hiPS-derived cardiomyocytes [74,75].…”

Section: Discussionmentioning

confidence: 99%

Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

Goßmann

Frotscher

Linder³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Common systems for the quantification of cellular contraction rely on animal-based models, complex experimental setups or indirect approaches. The herein presented CellDrum technology for testing mechanical tension of cellular monolayers and thin tissue constructs has the potential to scale-up mechanical testing towards medium-throughput analyses. Using hiPS-Cardiac Myocytes (hiPS-CMs) it represents a new perspective of drug testing and brings us closer to personalized drug medication. Methods: In the present study, monolayers of self-beating hiPS-CMs were grown on ultra-thin circular silicone membranes and deflect under the weight of the culture medium. Rhythmic contractions of the hiPS-CMs induced variations of the membrane deflection. The recorded contraction-relaxation-cycles were analyzed with respect to their amplitudes, durations, time integrals and frequencies. Besides unstimulated force and tensile stress, we investigated the effects of agonists and antagonists acting on Ca²⁺ channels (S-Bay K8644/verapamil) and Na⁺ channels (veratridine/lidocaine). Results: The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data. Conclusion: We conclude that the combination of the CellDrum with hiPS-CMs offers a fast, facile and precise system for pharmacological, toxicological studies and offers new preclinical basic research potential.

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Section: Discussionmentioning

confidence: 99%

Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

Goßmann

Frotscher

Linder³

et al. 2016

Cell Physiol Biochem

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“…Differentiation and purification of murine induced pluripotent stem cell-derived cardiomyocytes (iPSCM) is described elsewhere 16 . iPSCM at day 16 of differentiation were cultured on a 120-electrode microarray.…”

Section: Methodsmentioning

confidence: 99%

Myeloperoxidase Mediates Postischemic Arrhythmogenic Ventricular Remodeling

Mollenhauer

Friedrichs

Lange

et al. 2017

Circulation Research

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Rationale Ventricular arrhythmias remain the leading cause of death in patients suffering myocardial ischemia. Myeloperoxidase (MPO), a heme-enzyme released by polymorphonuclear neutrophils, accumulates within ischemic myocardium and has been linked to adverse left ventricular remodeling. Objective To reveal the role of MPO for the development of ventricular arrhythmias. Methods and Results In different murine models of myocardial ischemia MPO deficiency profoundly decreased vulnerability for ventricular tachycardia (VT) upon programmed right ventricular and burst stimulation and spontaneously as assessed by ECG telemetry following isoproterenol injection. Experiments employing CD11b/CD18-integrin-deficient (CD11b-/-) mice and intravenous MPO infusion revealed that neutrophil infiltration is a prerequisite for myocardial MPO accumulation. Ventricles from MPO-deficient (Mpo-/-) mice showed less pronounced slowing and decreased heterogeneity of electrical conduction in the periinfarct zone than WT mice. Expression of the redox sensitive gap-junctional protein connexin43 (Cx43) was reduced in the periinfarct area of WT compared to Mpo-/- mice. In isolated WT cardiomyocytes, Cx43 protein content decreased upon MPO/H2O2-incubation. Mapping of induced pluripotent stem-cell-derived cardiomyocyte (iPSCM) networks and in vivo investigations linked Cx43 breakdown to MPO-dependent activation of matrix-metalloproteinase 7. Moreover, Mpo-/- mice showed decreased ventricular postischemic fibrosis reflecting reduced accumulation of myofibroblasts. Ex vivo, MPO was demonstrated to induce fibroblast-to-myofibroblast transdifferentiation by activation of p38 mitogen-activated protein kinases (MAPK) resulting in upregulated collagen generation. In support of our experimental findings, baseline MPO plasma levels were independently associated with a history of ventricular arrhythmias, sudden cardiac death, or implantable cardioverter defibrillator implantation in a cohort of 2622 stable patients with an ejection fraction above 35% undergoing elective diagnostic cardiac evaluation. Conclusions MPO emerges as a crucial mediator of post-ischemic myocardial remodeling, and may evolve as a novel pharmacological target for secondary disease prevention following myocardial ischemia.

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“…For example, in diabetic rats, vitamin C decreased lipid peroxidation and increased the activities of antioxidant enzymes in the kidneys of diabetic rats, as well as reduced urinary albumin excretion (UAE), decreased kidney weight, and glomerular basement membrane (GBM) thickness [19]. It was reported that vitamin C protects kidney function and renal arterial reactivity against renal ischemic injury in mice [20] and vitamin C can induce cardiomyocytes differentiation of murine pluripotent stem cells through the synergistic effect of Wnt-signaling pathway [21]. Vitamin C has also been proven to function in vitamin E recycling and protect renal cells from apoptosis and senescence, increased regenerative ability of cells and fibrosis [22].…”

Section: Discussionmentioning

confidence: 99%

Gulo Acts as a de novo Marker for Pronephric Tubules in Xenopus laevis

Xie

Liu²,

Zhao³

et al. 2016

Kidney Blood Press Res

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Backgrounds/Aims: Vitamin C is an antioxidant and acts as a cofactor for several key enzymatic catalytic reactions in animals. Amphibians produce vitamin C in their kidneys, as opposed to mammals that produce vitamin C in their liver. Gulo serves as a crucial enzyme for vitamin C synthesis in mammals, but the characteristics and localization of its homologous genes during kidney development in Xenopus laevis, an amphibian, remains unknown. Methods: We aligned amino acid sequences of Gulo across different species by using bioinformatics methods and detected patterns of expression for Gulo during kidney development by using RT-PCR and in situ hybridization. Results: We identified a new site on the X. laevis genome, LOC495407. Sequence alignment analysis indicated this fragment is highly conserved and homologous to gulo genes in mammals. RT-PCR and in situ hybridization results reveal that X. laevis gulo is maternally expressed during the early stages of embryonic development, particularly, in the tubules of the pronephros from the middle tail-bud stage and onward in embryos. Conclusion: Gulo is a novel specific marker for pronephros tubules in X. laevis, and may be used as a potential marker for kidney development studies and disease diagnosis in mammals.

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Ascorbic Acid-Induced Cardiac Differentiation of Murine Pluripotent Stem Cells: Transcriptional Profiling and Effect of a Small Molecule Synergist of Wnt/β-Catenin Signaling Pathway

Cited by 26 publications

References 49 publications

Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

Myeloperoxidase Mediates Postischemic Arrhythmogenic Ventricular Remodeling

Gulo Acts as a <b><i>de novo</i></b> Marker for Pronephric Tubules in <b><i>Xenopus laevis</i></b>

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