Dataset Information

HiPSCs Derived Cardiac Cells for Drug and Toxicity Screening and Disease Modeling: What Micro- Electrode-Array Analyses Can Tell Us.

ABSTRACT: Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CM) have been intensively used in drug development and disease modeling. Since iPSC-cardiomyocyte (CM) was first generated, their characterization has become a major focus of research. Multi-/micro-electrode array (MEA) systems provide a non-invasive user-friendly platform for detailed electrophysiological analysis of iPSC cardiomyocytes including drug testing to identify potential targets and the assessment of proarrhythmic risk. Here, we provide a systematical overview about the physiological and technical background of micro-electrode array measurements of iPSC-CM. We introduce the similarities and differences between action- and field potential and the advantages and drawbacks of MEA technology. In addition, we present current studies focusing on proarrhythmic side effects of novel and established compounds combining MEA systems and iPSC-CM. MEA technology will help to open a new gateway for novel therapies in cardiovascular diseases while reducing animal experiments at the same time.

SUBMITTER: Kussauer S

PROVIDER: S-EPMC6912416 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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hiPSCs Derived Cardiac Cells for Drug and Toxicity Screening and Disease Modeling: What Micro- Electrode-Array Analyses Can Tell Us.

Kussauer Sophie S David Robert R Lemcke Heiko H

Cells 20191028 11

Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CM) have been intensively used in drug development and disease modeling. Since iPSC-cardiomyocyte (CM) was first generated, their characterization has become a major focus of research. Multi-/micro-electrode array (MEA) systems provide a non-invasive user-friendly platform for detailed electrophysiological analysis of iPSC cardiomyocytes including drug testing to identify potential targets and the assessment of proarrhythmic risk ...[more]

PMID: 31661896

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Project description:Nowadays, in vitro three-dimensional (3D) neuronal networks are becoming a consolidated experimental model to overcome most of the intrinsic limitations of bi-dimensional (2D) assemblies. In the 3D environment, experimental evidence revealed a wider repertoire of activity patterns, characterized by a modulation of the bursting features, than the one observed in 2D cultures. However, it is not totally clear and understood what pushes the neuronal networks towards different dynamical regimes. One possible explanation could be the underlying connectivity, which could involve a larger number of neurons in a 3D rather than a 2D space and could organize following well-defined topological schemes. Driven by experimental findings, achieved by recording 3D cortical networks organized in multi-layered structures coupled to Micro-Electrode Arrays (MEAs), in the present work we developed a large-scale computational network model made up of leaky integrate-and-fire (LIF) neurons to investigate possible structural configurations able to sustain the emerging patterns of electrophysiological activity. In particular, we investigated the role of the number of layers defining a 3D assembly and the spatial distribution of the connections within and among the layers. These configurations give rise to different patterns of activity that could be compared to the ones emerging from real in vitro 3D neuronal populations. Our results suggest that the introduction of three-dimensionality induced a global reduction in both firing and bursting rates with respect to 2D models. In addition, we found that there is a minimum number of layers necessary to obtain a change in the dynamics of the network. However, the effects produced by a 3D organization of the cells is somewhat mitigated if a scale-free connectivity is implemented in either one or all the layers of the network. Finally, the best matching of the experimental data is achieved supposing a 3D connectivity organized in structured bundles of links located in different areas of the 2D network.

Dataset Information

HiPSCs Derived Cardiac Cells for Drug and Toxicity Screening and Disease Modeling: What Micro- Electrode-Array Analyses Can Tell Us.

Publications

hiPSCs Derived Cardiac Cells for Drug and Toxicity Screening and Disease Modeling: What Micro- Electrode-Array Analyses Can Tell Us.

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