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番茄碱刺激人胚胎干细胞来源的心肌细胞成熟，用于模拟线粒体功能障碍。

Tomatidine-stimulated maturation of human embryonic stem cell-derived cardiomyocytes for modeling mitochondrial dysfunction.

机构信息

Department of Physiology, School of Medicine, Pusan National University, Yangsan, Republic of Korea.

Department of Physiology and Biophysics, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Republic of Korea.

出版信息

Exp Mol Med. 2022 Apr;54(4):493-502. doi: 10.1038/s12276-022-00746-8. Epub 2022 Apr 4.

DOI:10.1038/s12276-022-00746-8
PMID:35379934
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9076832/
Abstract

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.

摘要

人胚胎干细胞衍生的心肌细胞（hESC-CMs）已被报道表现出未成熟的胚胎或胎儿心肌细胞样表型。为了增强 hESC-CMs 的成熟度，我们鉴定出一种天然甾体生物碱，番茄碱，作为一种新的物质，刺激 hESC-CMs 的成熟。在心肌细胞分化过程中用番茄碱处理人胚胎干细胞可刺激几种心肌细胞特异性标志物的表达，并增加 T 小管的密度。此外，番茄碱处理增加了线粒体的数量和大小，并增强了线粒体层状嵴的形成。番茄碱处理刺激 hESC-CMs 中的线粒体功能，包括线粒体膜电位、氧化磷酸化和 ATP 产生。与对照细胞相比，番茄碱处理的 hESC-CMs 对阿霉素诱导的心脏毒性更敏感。总之，本研究表明，番茄碱通过加速线粒体生物发生和成熟促进干细胞向成体心肌细胞的分化，并且番茄碱处理的成熟 hESC-CMs 可用于心脏毒性筛选和心脏疾病建模。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dcd/9076832/412dd0242d76/12276_2022_746_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dcd/9076832/215b2384caec/12276_2022_746_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dcd/9076832/533c8bfbf97d/12276_2022_746_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dcd/9076832/521f50cc5912/12276_2022_746_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dcd/9076832/ee77d1e2a839/12276_2022_746_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dcd/9076832/1d00e48e2a9e/12276_2022_746_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dcd/9076832/412dd0242d76/12276_2022_746_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dcd/9076832/215b2384caec/12276_2022_746_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dcd/9076832/533c8bfbf97d/12276_2022_746_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dcd/9076832/521f50cc5912/12276_2022_746_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dcd/9076832/ee77d1e2a839/12276_2022_746_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dcd/9076832/1d00e48e2a9e/12276_2022_746_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dcd/9076832/412dd0242d76/12276_2022_746_Fig6_HTML.jpg

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2
Mitochondrial Determinants of Doxorubicin-Induced Cardiomyopathy.线粒体在多柔比星诱导性心肌病中的作用。
Circ Res. 2020 Mar 27;126(7):926-941. doi: 10.1161/CIRCRESAHA.119.314681. Epub 2020 Mar 26.
3
Cardiomyocyte maturation: advances in knowledge and implications for regenerative medicine.心肌细胞成熟：知识进展及其对再生医学的影响。
金@铂纳米颗粒增强小鼠胚胎干细胞来源及新生小鼠心肌细胞的成熟和收缩能力。
Tissue Eng Regen Med. 2025 May 20. doi: 10.1007/s13770-025-00724-x.
4
Modelling neurocardiac physiology and diseases using human pluripotent stem cells: current progress and future prospects.利用人类多能干细胞模拟神经心脏生理学和疾病：当前进展与未来展望
J Physiol. 2025 Mar;603(7):1865-1885. doi: 10.1113/JP286416. Epub 2024 Sep 5.
5
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Front Mol Med. 2023 Sep 1;3:1222986. doi: 10.3389/fmmed.2023.1222986. eCollection 2023.
6
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EMBO Rep. 2024 Apr;25(4):2015-2044. doi: 10.1038/s44319-024-00110-z. Epub 2024 Mar 13.
7
Switching of hypertrophic signalling towards enhanced cardiomyocyte identity and maturity by a GATA4-targeted compound.通过靶向 GATA4 的化合物转换肥厚信号以增强心肌细胞特性和成熟度。
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8
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