TY - JOUR
T1 - Biorealistic cardiac cell culture platforms with integrated monitoring of extracellular action potentials
AU - Trantidou, Tatiana
AU - Terracciano, Cesare M.
AU - Kontziampasis, Dimitrios
AU - Humphrey, Eleanor J.
AU - Prodromakis, Themistoklis
N1 - Funding Information:
This study was conducted with the financial support of the A.G. Leventis foundation and the British Heart Foundation. The authors would like to thank Dr Claudio Zuliani for his feedback on the electrode impedance measurements, Dr Rasheda Chowdhury for her support on the cell culturing and recording, Dr Despina Moschou for her assistance to the SEM imaging, and Mike Debney for developing the software application in MATLAB® to visualize the isochrones.
Copyright:
© 2015, The Author(s).
PY - 2015/6/8
Y1 - 2015/6/8
N2 - 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.
AB - 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.
KW - Biomaterials - cells
KW - Tissue engineering
UR - https://www.scopus.com/pages/publications/84930965728
U2 - 10.1038/srep11067
DO - 10.1038/srep11067
M3 - Article
C2 - 26053434
AN - SCOPUS:84930965728
SN - 2045-2322
VL - 5
JO - Scientific Reports
JF - Scientific Reports
M1 - 11067
ER -