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Nanomedicine. 2014 Jul;10(5):1065-73. doi: 10.1016/j.nano.2014.01.005. Epub 2014 Jan 31.

The arrhythmogenic effect of self-assembling nanopeptide hydrogel scaffolds on neonatal mouse cardiomyocytes.

Author information

1
Division of Cardiology, Department of Internal Medicine, Far-Eastern Memorial Hospital, New Taipei City, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
2
Institute of Pharmacology, School of Medicine, National Taiwan University, Taipei, Taiwan.
3
Division of Cardiology, Department of Internal Medicine, Far-Eastern Memorial Hospital, New Taipei City, Taiwan.
4
Graduate Institute of Clinical Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: ylho@ntu.edu.tw.

Abstract

The chaotic spatial disarray due to extracellular matrix expansion disrupts cardiomyocytes interaction and causes arrhythmia. We hypothesized that disordered nanopeptide scaffolds can mimic the chaotic spatial disarray related to cardiac fibrosis and have arrhythmogenic effects on cardiomyocytes. Primary mouse cardiomyocytes were cultured in 2D traditional and 3D nanopeptide hydrogel scaffold systems. Cardiomyocytes in 3D scaffolds showed irregular spontaneous contractile activity as compared with 2D culture controls. Calcium fluorimetric imaging revealed that basal intracellular calcium level increased 1.42-fold in cardiomyocytes cultured in the 3D scaffold, in vitro. The mRNA levels of sarcoplasmic reticulum calcium transport ATPase, ryanodine 2 receptor and connexin 43 elevated 2.14-fold, 2.33-fold and 2.62-fold in 3D compared with 2D. Immunofluorescence imaging revealed lateralization of the distribution of connexin 43 in 3D group. These findings suggest that 3D hydrogel culture system provides a model for the development of cardiac dysrhythmia. These limitations should be considered during cardiac tissue engineering.

FROM THE CLINICAL EDITOR:

This team of scientists has established a unique 3D hydrogel culture system as a model for the development of cardiac dysrhythmia.

KEYWORDS:

Arrhythmia; Cardiomyocyte; Connexin 43; Nanopeptide scaffold

PMID:
24491398
DOI:
10.1016/j.nano.2014.01.005
[Indexed for MEDLINE]
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