scholarly journals Syncytium cell growth increases Kir2.1 contribution in human iPSC-cardiomyocytes

2020 ◽  
Vol 319 (5) ◽  
pp. H1112-H1122 ◽  
Author(s):  
Weizhen Li ◽  
Julie L. Han ◽  
Emilia Entcheva
Keyword(s):  
Ion Channel ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Cell Contact ◽  
Isolated Cells ◽  
Protein Levels ◽  
Ion Channel Properties ◽  
Induced Pluripotent ◽  
Human Ipsc ◽  
Channel Properties

We identify cell culture density and cell-cell contact as an important factor in determining the expression of a key ion channel at the transcriptional and the protein levels, KCNJ2/Kir2.1, and its contribution to the electrophysiology of human induced pluripotent stem cell-derived cardiomyocytes. Our results indicate that studies on isolated cells, out of tissue context, may underestimate the cellular ion channel properties being characterized.

scholarly journals Ion Channel Expression and Characterization in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Zhihan Zhao ◽  
Huan Lan ◽  
Ibrahim El-Battrawy ◽  
Xin Li ◽  
Fanis Buljubasic ◽  
...  
Keyword(s):  
Stem Cell ◽  
Ion Channels ◽  
Ion Channel ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Biological Study ◽  
Adrenergic Stimulation ◽  
Cell Therapies ◽  
Channel Expression ◽  
Induced Pluripotent

Background. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are providing new possibilities for the biological study, cell therapies, and drug discovery. However, the ion channel expression and functions as well as regulations in hiPSC-CMs still need to be fully characterized. Methods. Cardiomyocytes were derived from hiPS cells that were generated from two healthy donors. qPCR and patch clamp techniques were used for the study. Results. In addition to the reported ion channels, INa, ICa-L, ICa-T, If, INCX, IK1, Ito, IKr, IKs IKATP, IK-pH, ISK1–3, and ISK4, we detected both the expression and currents of ACh-activated (KACh) and Na+-activated (KNa) K+, volume-regulated and calcium-activated (Cl-Ca) Cl−, and TRPV channels. All the detected ion currents except IK1, IKACh, ISK, IKNa, and TRPV1 currents contribute to AP duration. Isoprenaline increased ICa-L, If, and IKs but reduced INa and INCX, without an effect on Ito, IK1, ISK1–3, IKATP, IKr, ISK4, IKNa, ICl-Ca, and ITRPV1. Carbachol alone showed no effect on the tested ion channel currents. Conclusion. Our data demonstrate that most ion channels, which are present in healthy or diseased cardiomyocytes, exist in hiPSC-CMs. Some of them contribute to action potential performance and are regulated by adrenergic stimulation.

scholarly journals Human Induced Pluripotent Stem-Cell-Derived Cardiomyocytes as Models for Genetic Cardiomyopathies

2019 ◽  
Vol 20 (18) ◽  
pp. 4381 ◽  
Author(s):  
Andreas Brodehl ◽  
Hans Ebbinghaus ◽  
Marcus-André Deutsch ◽  
Jan Gummert ◽  
Anna Gärtner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Patient Specific ◽  
Promising Alternative ◽  
Human Ipscs ◽  
Genetic Landscape ◽  
Inherited Cardiomyopathies ◽  
Induced Pluripotent ◽  
Human Ipsc

In the last few decades, many pathogenic or likely pathogenic genetic mutations in over hundred different genes have been described for non-ischemic, genetic cardiomyopathies. However, the functional knowledge about most of these mutations is still limited because the generation of adequate animal models is time-consuming and challenging. Therefore, human induced pluripotent stem cells (iPSCs) carrying specific cardiomyopathy-associated mutations are a promising alternative. Since the original discovery that pluripotency can be artificially induced by the expression of different transcription factors, various patient-specific-induced pluripotent stem cell lines have been generated to model non-ischemic, genetic cardiomyopathies in vitro. In this review, we describe the genetic landscape of non-ischemic, genetic cardiomyopathies and give an overview about different human iPSC lines, which have been developed for the disease modeling of inherited cardiomyopathies. We summarize different methods and protocols for the general differentiation of human iPSCs into cardiomyocytes. In addition, we describe methods and technologies to investigate functionally human iPSC-derived cardiomyocytes. Furthermore, we summarize novel genome editing approaches for the genetic manipulation of human iPSCs. This review provides an overview about the genetic landscape of inherited cardiomyopathies with a focus on iPSC technology, which might be of interest for clinicians and basic scientists interested in genetic cardiomyopathies.

scholarly journals Modeling Neurological Disorders with Human Pluripotent Stem Cell-Derived Astrocytes

2019 ◽  
Vol 20 (16) ◽  
pp. 3862 ◽  
Author(s):  
Mika Suga ◽  
Takayuki Kondo ◽  
Haruhisa Inoue
Keyword(s):  
Stem Cell ◽  
Neurological Disorders ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Human Diseases ◽  
Human Pluripotent Stem Cell ◽  
Human Astrocytes ◽  
Induced Pluripotent ◽  
Human Ipsc

Astrocytes play vital roles in neurological disorders. The use of human induced pluripotent stem cell (iPSC)-derived astrocytes provides a chance to explore the contributions of astrocytes in human diseases. Here we review human iPSC-based models for neurological disorders associated with human astrocytes and discuss the points of each model.

scholarly journals The Emergence of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs) as a Platform to Model Arrhythmogenic Diseases

2020 ◽  
Vol 21 (2) ◽  
pp. 657 ◽  
Author(s):  
Marc Pourrier ◽  
David Fedida
Keyword(s):  
Stem Cell ◽  
Ion Channel ◽  
Pluripotent Stem Cell ◽  
Molecular Mechanisms ◽  
Induced Pluripotent Stem Cell ◽  
Transgenic Animal ◽  
Cardiac Diseases ◽  
Disease Phenotype ◽  
Induced Pluripotent

There is a need for improved in vitro models of inherited cardiac diseases to better understand basic cellular and molecular mechanisms and advance drug development. Most of these diseases are associated with arrhythmias, as a result of mutations in ion channel or ion channel-modulatory proteins. Thus far, the electrophysiological phenotype of these mutations has been typically studied using transgenic animal models and heterologous expression systems. Although they have played a major role in advancing the understanding of the pathophysiology of arrhythmogenesis, more physiological and predictive preclinical models are necessary to optimize the treatment strategy for individual patients. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have generated much interest as an alternative tool to model arrhythmogenic diseases. They provide a unique opportunity to recapitulate the native-like environment required for mutated proteins to reproduce the human cellular disease phenotype. However, it is also important to recognize the limitations of this technology, specifically their fetal electrophysiological phenotype, which differentiates them from adult human myocytes. In this review, we provide an overview of the major inherited arrhythmogenic cardiac diseases modeled using hiPSC-CMs and for which the cellular disease phenotype has been somewhat characterized.

scholarly journals E-Cadherin-Mediated Cell-Cell Contact Is Critical for Induced Pluripotent Stem Cell Generation

Stem Cells ◽  
2010 ◽  
Vol 28 (8) ◽  
pp. 1315-1325 ◽  
Author(s):  
Taotao Chen ◽  
Detian Yuan ◽  
Bin Wei ◽  
Jing Jiang ◽  
Jiuhong Kang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Cell Generation ◽  
Cell Contact ◽  
Induced Pluripotent ◽  
E Cadherin ◽  
Cell Cell

scholarly journals Modeling Group B Streptococcus and Blood-Brain Barrier Interaction by Using Induced Pluripotent Stem Cell-Derived Brain Endothelial Cells

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
Brandon J. Kim ◽  
Olivia B. Bee ◽  
Maura A. McDonagh ◽  
Matthew J. Stebbins ◽  
Sean P. Palecek ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tight Junctions ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Cell Models ◽  
Bacterial Interaction ◽  
Induced Pluripotent ◽  
Group B ◽  
Human Ipsc ◽  
First Time

ABSTRACT Here for the first time, human iPSC-derived BMECs were used to model bacterial interaction with the BBB. Unlike models previously used to study these interactions, iPSC-derived BMECs possess robust BBB properties, such as the expression of complex tight junctions that are key components for the investigation of bacterial effects on the BBB. Here, we demonstrated that GBS interacts with the iPSC-derived BMECs and specifically disrupts these tight junctions. Thus, using this BBB model may allow researchers to uncover novel mechanisms of BBB disruption during meningitis that are inaccessible to immortalized or primary cell models that lack substantial tight junctions. Bacterial meningitis is a serious infection of the central nervous system (CNS) that occurs after bacteria interact with and penetrate the blood-brain barrier (BBB). The BBB is comprised of highly specialized brain microvascular endothelial cells (BMECs) that function to separate the circulation from the CNS and act as a formidable barrier for toxins and pathogens. Certain bacteria, such as Streptococcus agalactiae (group B Streptococcus [GBS]), possess the ability to interact with and penetrate the BBB to cause meningitis. Modeling bacterial interaction with the BBB in vitro has been limited to primary and immortalized BMEC culture. While useful, these cells often do not retain BBB-like properties, and human primary cells have limited availability. Recently, a human induced pluripotent stem cell (iPSC)-derived BMEC model has been established that is readily renewable and retains key BBB phenotypes. Here, we sought to evaluate whether the iPSC-derived BMECs were appropriate for modeling bacterial interaction with the BBB. Using GBS as a model meningeal pathogen, we demonstrate that wild-type GBS adhered to, invaded, and activated the iPSC-derived BMECs, while GBS mutants known to have diminished BBB interaction were attenuated in the iPSC-derived model. Furthermore, bacterial infection resulted in the disruption of tight junction components ZO-1, occludin, and claudin-5. Thus, we show for the first time that the iPSC-derived BBB model can be utilized to study BBB interaction with a bacterial CNS pathogen. IMPORTANCE Here for the first time, human iPSC-derived BMECs were used to model bacterial interaction with the BBB. Unlike models previously used to study these interactions, iPSC-derived BMECs possess robust BBB properties, such as the expression of complex tight junctions that are key components for the investigation of bacterial effects on the BBB. Here, we demonstrated that GBS interacts with the iPSC-derived BMECs and specifically disrupts these tight junctions. Thus, using this BBB model may allow researchers to uncover novel mechanisms of BBB disruption during meningitis that are inaccessible to immortalized or primary cell models that lack substantial tight junctions.

scholarly journals NKX3-1 is required for induced pluripotent stem cell reprogramming and can replace OCT4 in mouse and human iPSC induction

2018 ◽  
Vol 20 (8) ◽  
pp. 900-908 ◽  
Author(s):  
Thach Mai ◽  
Glenn J. Markov ◽  
Jennifer J. Brady ◽  
Adelaida Palla ◽  
Hong Zeng ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Cell Reprogramming ◽  
Induced Pluripotent ◽  
Human Ipsc
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