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Biorealistic cardiac cell culture platforms with integrated monitoring of extracellular action potentials.

Trantidou T, Terracciano CM, Kontziampasis D, Humphrey EJ, Prodromakis T - Sci Rep (2015)

Bottom Line: Current platforms for in vitro drug development utilize confluent, unorganized monolayers of heart cells to study the effect on action potential propagation.However, standard cell cultures are of limited use in cardiac research, as they do not preserve important structural and functional properties of the myocardium.Our platform is compatible with existing read-out equipment and comprises a prompt method for more reliable CV studies.

View Article: PubMed Central - PubMed

Affiliation: 1] Nano group, ECS, University of Southampton, Southampton, United Kingdom [2] Centre for bio-inspired technology, Imperial College London, London, United Kingdom.

ABSTRACT
Current platforms for in vitro drug development utilize confluent, unorganized monolayers of heart cells to study the effect on action potential propagation. However, standard cell cultures are of limited use in cardiac research, as they do not preserve important structural and functional properties of the myocardium. Here we present a method to integrate a scaffolding technology with multi-electrode arrays and deliver a compact, off-the-shelf monitoring platform for growing biomimetic cardiac tissue. Our approach produces anisotropic cultures with conduction velocity (CV) profiles that closer resemble native heart tissue; the fastest impulse propagation is along the long axis of the aligned cardiomyocytes (CVL) and the slowest propagation is perpendicular (CVT), in contrast to standard cultures where action potential propagates isotropically (CVL ≈ CVT). The corresponding anisotropy velocity ratios (CVL/CVT = 1.38 - 2.22) are comparable with values for healthy adult rat ventricles (1.98 - 3.63). The main advantages of this approach are that (i) it provides ultimate pattern control, (ii) it is compatible with automated manufacturing steps and (iii) it is utilized through standard cell culturing protocols. Our platform is compatible with existing read-out equipment and comprises a prompt method for more reliable CV studies.

No MeSH data available.


Related in: MedlinePlus

Isochrones of action potential propagation.(a) MEA layout and corresponding isochrones of NRVM on unpatterned (control) and patterned MEAs when the culture was stimulated (b) from middle left (microelectrode #14), (c) from the center (microelectrode #44), (d) from middle right (microelectrode #84) (e) from top left (microelectrode #31) (f) from middle top (microelectrode #51) (g) from top right (microelectrode #71) (h) from bottom left (microelectrode #38), (i) from middle bottom (microelectrode #58) and (j) from bottom right (microelectrode #78).
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f3: Isochrones of action potential propagation.(a) MEA layout and corresponding isochrones of NRVM on unpatterned (control) and patterned MEAs when the culture was stimulated (b) from middle left (microelectrode #14), (c) from the center (microelectrode #44), (d) from middle right (microelectrode #84) (e) from top left (microelectrode #31) (f) from middle top (microelectrode #51) (g) from top right (microelectrode #71) (h) from bottom left (microelectrode #38), (i) from middle bottom (microelectrode #58) and (j) from bottom right (microelectrode #78).

Mentions: Figure 3 demonstrates representative isochrone maps of NRVM cultures on control and patterned MEAs (Fig. 3a) when stimulated from single electrodes located at nine distinct points at the cell culture area; middle left - electrode #14 (Fig. 3b), middle - electrode #44 (Fig. 3c), middle right - electrode #84 (Fig. 3d), top left - electrode #31 (Fig. 3e), middle top - electrode #51 (Fig. 3f), top right - electrode #71 (Fig. 3g), bottom left - electrode #38 (Fig. 3h), middle bottom - electrode #58 (Fig. 3i) and bottom right - electrode #78 (Fig. 3j). In four analyzed isotropic monolayers the corresponding velocity propagation profile revealed circular isochrones, showing uniform, smooth propagation throughout the culture, which agrees with previously reported studies14. Cell elongation and coalignment on the micro-engineered MEAs induced by oriented cell growth was followed by the fastest impulse propagation along the direction of the pattern, resulting in elliptical activation profiles best represented by Fig. 3c.


Biorealistic cardiac cell culture platforms with integrated monitoring of extracellular action potentials.

Trantidou T, Terracciano CM, Kontziampasis D, Humphrey EJ, Prodromakis T - Sci Rep (2015)

Isochrones of action potential propagation.(a) MEA layout and corresponding isochrones of NRVM on unpatterned (control) and patterned MEAs when the culture was stimulated (b) from middle left (microelectrode #14), (c) from the center (microelectrode #44), (d) from middle right (microelectrode #84) (e) from top left (microelectrode #31) (f) from middle top (microelectrode #51) (g) from top right (microelectrode #71) (h) from bottom left (microelectrode #38), (i) from middle bottom (microelectrode #58) and (j) from bottom right (microelectrode #78).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4459200&req=5

f3: Isochrones of action potential propagation.(a) MEA layout and corresponding isochrones of NRVM on unpatterned (control) and patterned MEAs when the culture was stimulated (b) from middle left (microelectrode #14), (c) from the center (microelectrode #44), (d) from middle right (microelectrode #84) (e) from top left (microelectrode #31) (f) from middle top (microelectrode #51) (g) from top right (microelectrode #71) (h) from bottom left (microelectrode #38), (i) from middle bottom (microelectrode #58) and (j) from bottom right (microelectrode #78).
Mentions: Figure 3 demonstrates representative isochrone maps of NRVM cultures on control and patterned MEAs (Fig. 3a) when stimulated from single electrodes located at nine distinct points at the cell culture area; middle left - electrode #14 (Fig. 3b), middle - electrode #44 (Fig. 3c), middle right - electrode #84 (Fig. 3d), top left - electrode #31 (Fig. 3e), middle top - electrode #51 (Fig. 3f), top right - electrode #71 (Fig. 3g), bottom left - electrode #38 (Fig. 3h), middle bottom - electrode #58 (Fig. 3i) and bottom right - electrode #78 (Fig. 3j). In four analyzed isotropic monolayers the corresponding velocity propagation profile revealed circular isochrones, showing uniform, smooth propagation throughout the culture, which agrees with previously reported studies14. Cell elongation and coalignment on the micro-engineered MEAs induced by oriented cell growth was followed by the fastest impulse propagation along the direction of the pattern, resulting in elliptical activation profiles best represented by Fig. 3c.

Bottom Line: Current platforms for in vitro drug development utilize confluent, unorganized monolayers of heart cells to study the effect on action potential propagation.However, standard cell cultures are of limited use in cardiac research, as they do not preserve important structural and functional properties of the myocardium.Our platform is compatible with existing read-out equipment and comprises a prompt method for more reliable CV studies.

View Article: PubMed Central - PubMed

Affiliation: 1] Nano group, ECS, University of Southampton, Southampton, United Kingdom [2] Centre for bio-inspired technology, Imperial College London, London, United Kingdom.

ABSTRACT
Current platforms for in vitro drug development utilize confluent, unorganized monolayers of heart cells to study the effect on action potential propagation. However, standard cell cultures are of limited use in cardiac research, as they do not preserve important structural and functional properties of the myocardium. Here we present a method to integrate a scaffolding technology with multi-electrode arrays and deliver a compact, off-the-shelf monitoring platform for growing biomimetic cardiac tissue. Our approach produces anisotropic cultures with conduction velocity (CV) profiles that closer resemble native heart tissue; the fastest impulse propagation is along the long axis of the aligned cardiomyocytes (CVL) and the slowest propagation is perpendicular (CVT), in contrast to standard cultures where action potential propagates isotropically (CVL ≈ CVT). The corresponding anisotropy velocity ratios (CVL/CVT = 1.38 - 2.22) are comparable with values for healthy adult rat ventricles (1.98 - 3.63). The main advantages of this approach are that (i) it provides ultimate pattern control, (ii) it is compatible with automated manufacturing steps and (iii) it is utilized through standard cell culturing protocols. Our platform is compatible with existing read-out equipment and comprises a prompt method for more reliable CV studies.

No MeSH data available.


Related in: MedlinePlus