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Research Paper|Volume 10, Issue 4|pp 532—548

A net-shaped multicellular formation facilitates the maturation of hPSC-derived cardiomyocytes through mechanical and electrophysiological stimuli

Taoyan Liu1,2, Chengwu Huang3,4, Hongxia Li1,2, Fujian Wu1,2, Jianwen Luo3,4, Wenjing Lu1,2, Feng Lan1,2
  • 1Beijing 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
  • 2Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China
  • 3Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China
  • 4Center for Biomedical Imaging Research, Tsinghua University, Beijing 100084, China
Received: February 4, 2020Accepted: April 9, 2018Published: April 14, 2018
https://doi.org/10.18632/aging.101411

Copyright: © 2018 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.