title: Biorealistic cardiac cell culture platforms with integrated monitoring of extracellular action potentials.
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.
authors.affiliation: 1] Nano group, ECS, University of Southampton, Southampton, United Kingdom [2] Centre for bio-inspired technology, Imperial College London, London, United Kingdom.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Trantidou
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Cesare M
authors.initials: CM
authors.lastname: Terracciano
authors.affiliation: Nano group, ECS, University of Southampton, Southampton, United Kingdom.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kontziampasis
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Eleanor J
authors.initials: EJ
authors.lastname: Humphrey
authors.affiliation: 1] Nano group, ECS, University of Southampton, Southampton, United Kingdom [2] Centre for bio-inspired technology, Imperial College London, London, United Kingdom.
authors.forename: Themistoklis
authors.initials: T
authors.lastname: Prodromakis
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D016880:Anisotropy; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002478:Cells, Cultured; D017097:Electric Impedance; D006329:Heart Conduction System / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley