Nøvik Steffen, Hirayama-Shoji Kayoko, Combriat Thomas, Sakalys Domantas, Aashamar Erik, Louch William E, Häfliger Philipp Dominik, Krauss Stefan Johannes Karl, Martinsen Ørjan Grøttem
Department of Informatics, University of Oslo, Oslo 0316, Norway; Hybrid Technology Hub, Institute of Basic Medical Sciences, University of Oslo, Oslo 0372, Norway.
Hybrid Technology Hub, Institute of Basic Medical Sciences, University of Oslo, Oslo 0372, Norway.
Biosens Bioelectron. 2025 Nov 1;287:117634. doi: 10.1016/j.bios.2025.117634. Epub 2025 Jul 3.
Engineered heart tissues (EHTs), composed of human stem cell-derived cardiomyocytes and fibroblasts, have emerged as promising tools for disease modeling and drug discovery due to their ability to replicate aspects of the function and structure of the heart muscle. While bioimpedance and electrophysiology measurements are powerful tools for monitoring EHTs, these techniques can be challenging to perform due to the high conductivity of the surrounding cell medium. In this study, we explored the possibility of measuring bioimpedance and electrophysiology outside of the cell medium. To this end, we developed a platform that lifts EHTs from the culture medium during the measurements, thereby allowing the electrical current to flow directly through the tissues. The platform monitors contractility by fixed frequency impedance measurements, electrophysiology by field potential measurements, and structural changes through electrical impedance spectroscopy. Over two weeks of measurements, we observed increasing trends in contractility and field potential amplitudes, along with structural changes. No adverse effect on the EHTs were detected, ensuring their stability and viability throughout the monitoring process. Moreover, the impedance amplitude measured on the platform correlates with the contractile degree during drug experiments, serving as a reliable indicator of EHT functionality. Electrical stimulation with limited charge injection was also demonstrated. In conclusion, our platform offers a comprehensive and efficient method for monitoring EHTs and holds potential as a tool for cardiovascular disease modeling and drug screening.
工程化心脏组织(EHTs)由人类干细胞衍生的心肌细胞和成纤维细胞组成,因其能够复制心肌功能和结构的某些方面,已成为疾病建模和药物发现的有前途的工具。虽然生物阻抗和电生理学测量是监测EHTs的有力工具,但由于周围细胞培养基的高导电性,这些技术实施起来可能具有挑战性。在本研究中,我们探索了在细胞培养基外测量生物阻抗和电生理学的可能性。为此,我们开发了一个平台,在测量过程中将EHTs从培养基中提起,从而使电流直接流过组织。该平台通过固定频率阻抗测量监测收缩性,通过场电位测量监测电生理学,并通过电阻抗光谱监测结构变化。在两周的测量中,我们观察到收缩性和场电位幅度呈上升趋势,同时伴有结构变化。未检测到对EHTs有不利影响,确保了它们在整个监测过程中的稳定性和活力。此外,在平台上测量的阻抗幅度与药物实验期间的收缩程度相关,可作为EHT功能的可靠指标。还展示了有限电荷注入的电刺激。总之,我们的平台为监测EHTs提供了一种全面而有效的方法,有望成为心血管疾病建模和药物筛选的工具。