On-chip constructive cell-Network study (I): Contribution of cardiac fibroblasts to cardiomyocyte beating synchronization and community effect

<p>Abstract</p> <p>Backgrounds</p> <p>To clarify the role of cardiac fibroblasts in beating synchronization, we have made simple lined-up cardiomyocyte-fibroblast network model in an on-chip single-cell-based cultivation system.</p> <p>Results</p> <p>The synchronization phenomenon of two cardiomyocyte networks connected by fibroblasts showed (1) propagation velocity of electrophysiological signals decreased a magnitude depending on the increasing number of fibroblasts, not the lengths of fibroblasts; (2) fluctuation of interbeat intervals of the synchronized two cardiomyocyte network connected by fibroblasts did not always decreased, and was opposite from homogeneous cardiomyocyte networks; and (3) the synchronized cardiomyocytes connected by fibroblasts sometimes loses their synchronized condition and recovered to synchronized condition, in which the length of asynchronized period was shorter less than 30 beats and was independent to their cultivation time, whereas the length of synchronized period increased according to cultivation time.</p> <p>Conclusions</p> <p>The results indicated that fibroblasts can connect cardiomyocytes electrically but do not significantly enhance and contribute to beating interval stability and synchronization. This might also mean that an increase in the number of fibroblasts in heart tissue reduces the cardiomyocyte 'community effect', which enhances synchronization and stability of their beating rhythms.</p

On-chip constructive cell-network study (II): on-chip quasi-in vivo cardiac toxicity assay for ventricular tachycardia/fibrillation measurement using ring-shaped closed circuit microelectrode with lined-up cardiomyocyte cell network

<p>Abstract</p> <p>Backgrounds</p> <p>Conventional <it>in vitro </it>approach using human ether-a-go-go related gene (hERG) assay has been considered worldwide as the first screening assay for cardiac repolarization safety. However, it does not always oredict the potential QT prolongation risk or pro-arrhythmic risk correctly. For adaptable preclinical strategiesto evaluate global cardiac safety, an on-chip quasi-<it>in vivo </it>cardiac toxicity assay for lethal arrhythmia (ventricular tachyarrhythmia) measurement using ring-shaped closed circuit microelectrode chip has been developed.</p> <p>Results</p> <p>The ventricular electrocardiogram (ECG)-like field potential data, which includes both the repolarization and the conductance abnormality, was acquired from the self-convolutied extracellular field potentials (FPs) of a lined-up cardiomyocyte network on a circle-shaped microelectrode in an agarose microchamber. When Astemisol applied to the closed-loop cardiomyocyte network, self-convoluted FP profile of normal beating changed into an early afterdepolarization (EAD) like waveform, and then showed ventricular tachyarrhythmias and ventricular fibrilations (VT/Vf). QT-prolongation-like self-convoluted FP duration prolongation and its fluctuation increase was also observed according to the increase of Astemizole concentration.</p> <p>Conclusions</p> <p>The results indicate that the convoluted FPs of the quasi<it>-in vivo </it>cell network assay includes both of the repolarization data and the conductance abnormality of cardiomyocyte networks has the strong potential to prediction lethal arrhythmia.</p

Microtechnologies to fuel neurobiological research with nanometer precision

The interface between engineering and molecular life sciences has been fertile ground for advancing our understanding of complex biological systems. Engineered microstructures offer a diverse toolbox for cellular and molecular biologists to direct the placement of cells and small organisms, and to recreate biological functions in vitro: cells can be positioned and connected in a designed fashion, and connectivity and community effects of cells studied. Because of the highly polar morphology and finely compartmentalized functions of neurons, microfabricated cell culture systems and related on-chip technologies have become an important enabling platform for studying development, function and degeneration of the nervous system at the molecular and cellular level. Here we review some of the compartmentalization techniques developed so far to highlight how high- precision control of neuronal connectivity allows new approaches for studying axonal and synaptic biology.Peer reviewe

Quasi-In vivo Heart Electrocardiogram Measurement of ST Period Using Convolution of Cell Network Extracellular Field Potential Propagation in Lined-Up Cardiomyocyte Cell-Network Circuit

A model for the quasi-in vivo heart electrocardiogram (ECG) measurement of the ST period has been developed. As the part of ECG data at the ST period is the convolution of the extracellular field potentials (FPs) of cardiomyocytes in a ventricle, we have fabricated a lined-up cardiomyocyte cell-network on a lined-up microelectrode array and a circular microelectrode in an agarose microchamber, and measured the convoluted FPs. When the ventricular tachyarrhythmias of beating occurred in the cardiomyocyte network, the convoluted FP profile showed similar arrhythmia ECG-like profiles, indicating the convoluted FPs of the in vitro cell network include both the depolarization data and the propagation manner of beating in the heart. </jats:p