机构：[1]Beijing Laboratory for Cardiovascular Precision Medicine, The Key Laboratory of Remodeling‐Related Cardiovascular Disease, Ministry of Education, Beijing Collaborative Innovation Center for Cardiovascular Disorders, Anzhen Hospital, Capital Medical University, Beijing 100029, China临床科室心脏内科中心首都医科大学附属安贞医院[2]Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China首都医科大学附属安贞医院[3]Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China[4]Center for Biomedical Imaging Research, Tsinghua University, Beijing 100084, China
The use of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is limited in drug discovery and cardiac disease mechanism studies due to cell immaturity. Although many approaches have been reported to improve the maturation of hiPSC-CMs, the elucidation of the process of maturation is crucial. We applied a small-molecule-based differentiation method to generate cardiomyocytes (CMs) with multiple aggregation forms. The motion analysis revealed significant physical differences in the differently shaped CMs, and the net-shaped CMs had larger motion amplitudes and faster velocities than the sheet-shaped CMs. The net-shaped CMs displayed accelerated maturation at the transcriptional level and were more similar to CMs with a prolonged culture time (30 days) than to sheet-d15. Ion channel genes and gap junction proteins were up-regulated in net-shaped CMs, indicating that robust contraction was coupled with enhanced ion channel and connexin expression. The net-shaped CMs also displayed improved myofibril ultrastructure under transmission electron microscopy. In conclusion, different multicellular hPSC-CM structures, such as the net-shaped pattern, are formed using the conditioned induction method, providing a useful tool to improve cardiac maturation.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81570215, 81422003]
第一作者机构：[1]Beijing Laboratory for Cardiovascular Precision Medicine, The Key Laboratory of Remodeling‐Related Cardiovascular Disease, Ministry of Education, Beijing Collaborative Innovation Center for Cardiovascular Disorders, Anzhen Hospital, Capital Medical University, Beijing 100029, China[2]Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China
通讯作者：
通讯机构：[1]Beijing Laboratory for Cardiovascular Precision Medicine, The Key Laboratory of Remodeling‐Related Cardiovascular Disease, Ministry of Education, Beijing Collaborative Innovation Center for Cardiovascular Disorders, Anzhen Hospital, Capital Medical University, Beijing 100029, China[2]Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China
推荐引用方式(GB/T 7714)：
Liu Taoyan,Huang Chengwu,Li Hongxia,et al.A net-shaped multicellular formation facilitates the maturation of hPSC-derived cardiomyocytes through mechanical and electrophysiological stimuli[J].AGING-US.2018,10(4):532-548.doi:10.18632/aging.101411.
APA：
Liu, Taoyan,Huang, Chengwu,Li, Hongxia,Wu, Fujian,Luo, Jianwen...&Lan, Feng.(2018).A net-shaped multicellular formation facilitates the maturation of hPSC-derived cardiomyocytes through mechanical and electrophysiological stimuli.AGING-US,10,(4)
MLA：
Liu, Taoyan,et al."A net-shaped multicellular formation facilitates the maturation of hPSC-derived cardiomyocytes through mechanical and electrophysiological stimuli".AGING-US 10..4(2018):532-548
