Department of Mechanical Engineering, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, 223-8522, Japan.
Division of Advanced Mechanical Systems Engineering, Institute of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei-shi, Tokyo, 184-8588, Japan.
Adv Healthc Mater. 2024 Oct;13(27):e2303477. doi: 10.1002/adhm.202303477. Epub 2024 May 29.
Here an electrical stimulation system is described for maturing microfiber-shaped cardiac tissue (cardiac microfibers, CMFs). The system enables stable culturing of CMFs with electrical stimulation by placing the tissue between electrodes. The electrical stimulation device provides an electric field covering whole CMFs within the stimulation area and can control the beating of the cardiac microfibers. In addition, CMFs under electrical stimulation with different frequencies are examined to evaluate the maturation levels by their sarcomere lengths, electrophysiological characteristics, and gene expression. Sarcomere elongation (14% increase compared to control) is observed at day 10, and a significant upregulation of electrodynamic properties such as gap junction protein alpha 1 (GJA1) and potassium inwardly rectifying channel subfamily J member 2 (KCNJ2) (maximum fourfold increase compared to control) is observed at day 30. These results suggest that electrically stimulated cultures can accelerate the maturation of microfiber-shaped cardiac tissues compared to those without electrical stimulation. This model will contribute to the pathological research of unexplained cardiac diseases and pharmacologic testing by stably constructing matured CMFs.
这里描述了一种用于成熟微纤维状心肌组织（心肌微纤维，CMFs）的电刺激系统。该系统通过将组织置于电极之间，实现了 CMFs 的稳定电刺激培养。电刺激装置提供了覆盖刺激区域内整个 CMFs 的电场，并能控制心肌微纤维的跳动。此外，通过检测不同频率电刺激下的 CMFs，观察到肌节长度、电生理特性和基因表达的成熟度水平的变化。在第 10 天观察到肌节伸长（与对照组相比增加 14%），在第 30 天观察到电动力学特性（如缝隙连接蛋白 alpha 1（GJA1）和内向整流钾通道亚家族 J 成员 2（KCNJ2））的显著上调（与对照组相比最大增加四倍）。这些结果表明，与未经电刺激的培养相比，电刺激培养可以加速微纤维状心肌组织的成熟。该模型将通过稳定构建成熟的 CMFs 为不明原因的心脏疾病的病理研究和药物测试做出贡献。
