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

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 maturatio...

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Published inAging (Albany, NY.) Vol. 10; no. 4; pp. 532 - 548
Main Authors Liu, Taoyan, Huang, Chengwu, Li, Hongxia, Wu, Fujian, Luo, Jianwen, Lu, Wenjing, Lan, Feng
Format Journal Article
LanguageEnglish
Published United States Impact Journals 14.04.2018
Subjects
Cell Differentiation - physiology
Electric Stimulation
Humans
Induced Pluripotent Stem Cells - cytology
Induced Pluripotent Stem Cells - metabolism
Myocytes, Cardiac - cytology
Myocytes, Cardiac - metabolism
Research Paper
Stress, Mechanical
Tissue Engineering - methods
maturation
cardiac differentiation
cardiomyocyte clusters
ultrastructure
hiPSC
motion analysis
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Summary: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.
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ISSN:1945-4589
1945-4589
DOI:10.18632/aging.101411