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Cyclic Stretching Induces Maturation of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes through Nuclear-Mechanotransduction

Authors
Song, MyeongjinJang, YongjunKim, Seung-JongPark, Yongdoo
Issue Date
Aug-2022
Publisher
한국조직공학과 재생의학회
Keywords
Tensile force; Cyclic stretch; Cardiomyocyte; Maturation; Nuclear-mechanotransduction
Citation
Tissue Engineering and Regenerative Medicine, v.19, no.4, pp.781 - 792
Indexed
SCIE
SCOPUS
KCI
Journal Title
Tissue Engineering and Regenerative Medicine
Volume
19
Number
4
Start Page
781
End Page
792
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/55450
DOI
10.1007/s13770-021-00427-z
ISSN
1738-2696
Abstract
Background: During cardiogenesis, cardiac cells receive various stimuli, such as biomechanical and chemical cues, from the surrounding microenvironment, and these signals induce the maturation of heart cells. Mechanical force, especially tensile force in the heart, is one of the key stimuli that induce cardiomyocyte (CM) maturation through mechanotransduction, a process through which physical cues are transformed into biological responses. However, the effects and mechanisms of tensile force on cell maturation are poorly studied. Methods: In this study, we developed a cyclic stretch system that mimics the mechanical environment of the heart by loading tensile force to human-induced pluripotent stem cell (hiPSC)-derived CMs. hiPSC-CMs cultured with the cyclic stretch system analyzed morphological change, immunofluorescent staining, expression of maturation markers in mRNA, and beating properties compared to static cultures. Results: hiPSC-CMs cultured with the cyclic stretch system showed increased cell alignment, sarcomere length and expression of maturation markers in mRNA, such as TNNI3, MYL2 and TTN, compared to static cultures. Especially, the expression of genes related to nuclear mechanotransduction, such as Yap1, Lamin A/C, plectin, and desmin, was increased in the cyclically stretched hiPSC-CMs. Furthermore, the volume of the nucleus was increased by as much as 120% in the cyclic stretch group. Conclusion: These results revealed that nuclear mechanotransduction induced by tensile force is involved in CM maturation. Together, these findings provide novel evidence suggesting that nuclear mechanotransduction induced by tensile force is involved in the regulation of cardiac maturation.
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1. Basic Science > Department of Biomedical Engineering > 1. Journal Articles
4. Research institute > Stem Cell Institute > 1. Journal Articles

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