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KMID : 0620920220540040493
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Experimental & Molecular Medicine
2022 Volume.54 No. 4 p.493 ~ p.502
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Tomatidine-stimulated maturation of human embryonic stem cell-derived cardiomyocytes for modeling mitochondrial dysfunction
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Kim Ye-Seul
Yoon Jung-Won
Kim Da-Sol
Choi Seung-Hak
Kim Hyoung-Kyu
Youm Jae-Boum
Han Jin
Heo Soon-Chul
Hyun Sung-Ae
Seo Jung-Wook
Kim Deok-Ho
Kim Jae-Ho
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Abstract
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Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) have been reported to exhibit immature embryonic or fetal cardiomyocyte-like phenotypes. To enhance the maturation of hESC-CMs, we identified a natural steroidal alkaloid, tomatidine, as a new substance that stimulates the maturation of hESC-CMs. Treatment of human embryonic stem cells with tomatidine during cardiomyocyte differentiation stimulated the expression of several cardiomyocyte-specific markers and increased the density of T-tubules. Furthermore, tomatidine treatment augmented the number and size of mitochondria and enhanced the formation of mitochondrial lamellar cristae. Tomatidine treatment stimulated mitochondrial functions, including mitochondrial membrane potential, oxidative phosphorylation, and ATP production, in hESC-CMs. Tomatidine-treated hESC-CMs were more sensitive to doxorubicin-induced cardiotoxicity than the control cells. In conclusion, the present study suggests that tomatidine promotes the differentiation of stem cells to adult cardiomyocytes by accelerating mitochondrial biogenesis and maturation and that tomatidine-treated mature hESC-CMs can be used for cardiotoxicity screening and cardiac disease modeling.
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KEYWORD
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Embryonic stem cells, Heart failure, Stem-cell differentiation
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