Conduction block in micropatterned cardiomyocyte cultures replicating the structure of ventricular cross-sections

Badie, Nima; Scull, James A.; Klinger, Rebecca Y.; Krol, Ava; Bursac, Nenad

doi:10.1093/cvr/cvr304

Cited by 20 publications

(29 citation statements)

References 28 publications

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“…To investigate the roles of cardiac micro- and macrostructure in action potential conduction in vitro , we previously combined high-resolution cell micropatterning and diffusion tensor magnetic resonance imaging (DTMRI) to create 2-D cultures (monolayers) of neonatal rat cardiomyocytes replicating realistic structure of ventricular tissue [5]. Electrophysiological studies in these cultures revealed that intrinsic variations in intramural cardiac fiber orientation underlie the spatial non-uniformity of action potential conduction and directly determine the likelihood, location, and spatiotemporal dynamics of conduction block [6, 7]. …”

Section: Introductionmentioning

confidence: 99%

Robust T-tubulation and maturation of cardiomyocytes using tissue-engineered epicardial mimetics

et al. 2014

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Complex three-dimensional (3-D) heart structure is an important determinant of cardiac electrical and mechanical function. In this study, we set to develop a versatile tissue-engineered system that can promote important aspects of cardiac functional maturation and reproduce variations in myofiber directions present in native ventricular epicardium. We cultured neonatal rat cardiomyocytes within a 3-D hydrogel environment using microfabricated elastomeric molds with hexagonal posts. By varying individual post orientations along the directions derived from diffusion tensor magnetic resonance imaging (DTMRI) maps of human ventricle, we created large (2.5 × 2.5 cm2) 3-D cardiac tissue patches with cardiomyocyte alignment that replicated human epicardial fiber orientations. After 3 weeks of culture, the advanced structural and functional maturation of the engineered 3-D cardiac tissues compared to age-matched 2-D monolayers was evident from: 1) the presence of dense, aligned and electromechanically-coupled cardiomyocytes, quiescent fibroblasts, and interspersed capillary-like structures, 2) action potential propagation with near-adult conduction velocity and directional dependence on local cardiomyocyte orientation, and 3) robust formation of T-tubules aligned with Z-disks, co-localization of L-type Ca2+ channels and ryanodine receptors, and accelerated Ca2+ transient kinetics. This biomimetic tissue-engineered platform can enable systematic in vitro studies of cardiac structure-function relationships and promote the development of advanced tissue engineering strategies for cardiac repair and regeneration.

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Section: Introductionmentioning

confidence: 99%

Robust T-tubulation and maturation of cardiomyocytes using tissue-engineered epicardial mimetics

et al. 2014

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“…Diverse behaviours can be observed in networks of connected elements including a variety of synchronous regimes, pattern formation, spiral wave propagation, and spatio-temporal chaos. An example of a physiologically-relevant system is the monolayer cultures of neonatal rat ventricular myocytes (NRVMs) that is often used as experimental models in studies on multicellular cardiac electrophysiology [5][6][7][8]. These monolayers usually exhibit electrical automaticity [9][10][11], defined as the ability to generate action potentials without external (electrical, mechanical, or chemical) stimulations.…”

Section: Introductionmentioning

confidence: 99%

Multicellular automaticity of cardiac cell monolayers: effects of density and spatial distribution of pacemaker cells

et al. 2014

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The biological pacemaker approach is an alternative to cardiac electronic pacemakers. Its main objective is to create pacemaking activity from added or modified distribution of spontaneous cells in the myocardium. This paper aims to assess how automaticity strength of pacemaker cells (i.e. their ability to maintain robust spontaneous activity with fast rate and to drive neighboring quiescent cells) and structural linear anisotropy, combined with density and spatial distribution of pacemaker cells, may affect the macroscopic behavior of the biological pacemaker. A stochastic algorithm was used to randomly distribute pacemaker cells, with various densities and spatial distributions, in a semi-continuous mathematical model. Simulations of the model showed that stronger automaticity allows onset of spontaneous activity for lower densities and more homogeneous spatial distributions, displayed more central foci, less variability in cycle lengths and synchronization of electrical activation for similar spatial patterns, but more variability in those same variables for dissimilar spatial patterns. Compared to their isotropic counterparts, in silico anisotropic monolayers had less central foci and displayed more variability in cycle lengths and synchronization of electrical activation for both similar and dissimilar spatial patterns. The present study established a link between microscopic structure and macroscopic behavior of the biological pacemaker, and may provide crucial information for optimized biological pacemaker therapies.

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“…Hence, to supply sufficient oxygen and nutrients to sustain cells located deep within the 3D tissue construct with a porous or vascular network is a great challenge. [236][237][238][239][240][241] Current engineered 3D tissues are developed to culture cells within biodegradable natural or synthetic scaffolds. [242][243][244][245] Cells grow in these engineered scaffolds which function as 3D structures.…”

Section: Applications In Tissue Engineering and Regenerative Medicinementioning

confidence: 99%

The Role of Nanotechnology in Induced Pluripotent and Embryonic Stem Cells Research

Chen¹,

Qiu²,

Li³

2014

j biomed nanotechnol

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This paper reviews the recent studies on development of nanotechnology in the field of induced pluripotent and embryonic stem cells. Stem cell therapy is a promising therapy that can improve the quality of life for patients with refractory diseases. However, this option is limited by the scarcity of tissues, ethical problem, and tumorigenicity. Nanotechnology is another promising therapy that can be used to mimic the extracellular matrix, label the implanted cells, and also can be applied in the tissue engineering. In this review, we briefly introduce implementation of nanotechnology in induced pluripotent and embryonic stem cells research. Finally, the potential application of nanotechnology in tissue engineering and regenerative medicine is also discussed.

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Conduction block in micropatterned cardiomyocyte cultures replicating the structure of ventricular cross-sections

Abstract: Our study suggests that specific micro- and macrostructural features of the ventricle determine the incidence and spatiotemporal characteristics of conduction block, independent of spatial heterogeneities in ion channel expression.

Cited by 20 publications

References 28 publications

Robust T-tubulation and maturation of cardiomyocytes using tissue-engineered epicardial mimetics

Robust T-tubulation and maturation of cardiomyocytes using tissue-engineered epicardial mimetics

Multicellular automaticity of cardiac cell monolayers: effects of density and spatial distribution of pacemaker cells

The Role of Nanotechnology in Induced Pluripotent and Embryonic Stem Cells Research

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