Living myocardial slices: Advancing arrhythmia research

Abstract

Living myocardial slices (LMS) are ultrathin (150–400 µm) sections of intact myocardium that can be used as a comprehensive model for cardiac arrhythmia research. The recent introduction of biomimetic electromechanical cultivation chambers enables long-term cultivation and easy control of living myocardial slices culture conditions. The aim of this review is to present the potential of this biomimetic interface using living myocardial slices in electrophysiological studies outlining advantages, disadvantages and future perspectives of the model. Furthermore, different electrophysiological techniques and their application on living myocardial slices will be discussed. The developments of living myocardial slices in electrophysiology research will hopefully lead to future breakthroughs in the understanding of cardiac arrhythmia mechanisms and the development of novel therapeutic options.

Biomimetic cultivation of atrial tissue slices as novel platform for in-vitro atrial arrhythmia studies

“…This model shows high in-vivo representativeness, due to the use of human specimen which maintain 3D architecture with intact cellular interconnections and cell–cell communication. Moreover, LMS from patients with arrhythmia enable the opportunity to directly study the effect of atrial arrhythmias, including AF, on structural and electrical remodeling in a petri-dish 2 .…”

“…Living myocardial slices (LMS) are ultra-thin sections of intact human myocardium, which are presented as a novel model for translational research 1 , 2 . LMS overcome most limitations of conventional myocardial cell cultures and allow for a high degree of in-vivo representativeness, due to the maintained 3D architecture and intact cell–cell interactions of human cardiac biopsies 1 .…”

Towards Improved Human In Vitro Models for Cardiac Arrhythmia: Disease Mechanisms, Treatment, and Models of Atrial Fibrillation

“…However, the generation of patient-specific disease models is more challenging, and the associated high investment to produce the lines make them less attractive for disease modeling [ 113 , 114 ]. In addition, the use of living myocardial slices has been an important approach for studying several aspects of AFib over the last years [ 115 , 116 , 117 , 118 ]. Since they retain the cellular architecture and connections found in the heart, mechanisms related to electrophysiology, fibrosis, or calcium handling can be studied.…”

Commentary: Acute effects of cardiac contractility modulation stimulation in conventional 2D and 3D human induced pluripotent stem cell-derived cardiomyocyte models

“…LMS are ultra-thin (300 µm) sections of intact cardiac tissue that maintain structural integrity with intact cellular connections, extracellular matrix proteins and heterocellularity, as they are directly prepared from patient biopsies with a high-precision vibratome ( Schneider-Warme et al, 2018 ; Amesz et al, 2023 ). LMS are cultured in custom-made biomimetic cultivation chambers at 37°C with near-physiological preload of 1 mN, corresponding to a mean diastolic wall stress of 0.66 kN/m 2 ( Fischer et al, 2019 ; Amesz et al, 2023 ). Electrical stimulation is established with graphite field electrodes, leading to cardiac contraction of the LMS ( Fischer et al, 2019 ; Amesz et al, 2023 ).…”

“…LMS are cultured in custom-made biomimetic cultivation chambers at 37°C with near-physiological preload of 1 mN, corresponding to a mean diastolic wall stress of 0.66 kN/m 2 ( Fischer et al, 2019 ; Amesz et al, 2023 ). Electrical stimulation is established with graphite field electrodes, leading to cardiac contraction of the LMS ( Fischer et al, 2019 ; Amesz et al, 2023 ). In comparison to 3D-ECT, LMS represent more accurate in-vivo mimicry, because the complex microarchitecture of the cardiac system including all cell types and extracellular matrix proteins is difficult to mimic in-vitro , and hiPSC-CMs often fail to show complete cardiac maturity ( Qu et al, 2020 ).…”