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.
Highlights
The first generation of induced pluripotent stem cells by Yamanka and co-workers in 2006 was a milestone for stem cell research as it allows the in vitro production of human cells without ethical concerns
Successful pre-clinical application of induced pluripotent stem cell (iPSC)-derived cardiomyocytes for drug screening assays has been lately demonstrated by the CiPA initiative, which was initiated to assess the proarrhythmic risk of novel cardio therapeutics
A common micro-electrode array (MEA) system is composed of dot-like electrodes arranged in two-dimensional grids that measure the fluctuations in the extracellular field potential (FP) of an attached cell layer in respect to a reference electrode placed outside the grid (Figure 1)
Summary
The first generation of induced pluripotent stem cells (iPSCs) by Yamanka and co-workers in 2006 was a milestone for stem cell research as it allows the in vitro production of human cells without ethical concerns. One possible application for iPSC-derived cardiomyocytes (CMs) is their use in cell therapy replacing damaged tissue by in vitro generated CMs. As cardiovascular diseases are the major cause of death worldwide such regenerative approaches are needed for the development of novel treatment options. Thereby, an important future option of iPSC-CMs will be their generation from patient specific tissue enabling the implementation of autologous cell transplantation strategies. In this respect, iPSC-CMs can be used for the development of personalized drug screening approaches and clinically relevant diseases models. A myriad of studies investigated in vitro drug effects on different ion channels of iPSC-CMs [8,9,10,11], reflecting the importance of electrophysiological measurements using stem cell derived cardiac cells. Typical approaches to investigate the electrophysiological properties of stem cell derived CMs will be discussed in the following paragraph
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