阿霉素致人诱导性多潜能干细胞来源的心肌细胞损伤模型的建立

崔宁 柯兵兵 吴福建 白蕊 刘涛燕 李蕾 兰峰 崔鸣*

doi:10.16098/j.issn.0529-1356.2018.03.007

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解剖学报 ›› 2018, Vol. 49 ›› Issue (3) : 309-316. DOI: 10.16098/j.issn.0529-1356.2018.03.007

细胞和分子生物学

阿霉素致人诱导性多潜能干细胞来源的心肌细胞损伤模型的建立

崔宁¹ 柯兵兵²吴福建³ 白蕊³刘涛燕³ 李蕾¹兰峰³崔鸣^1*

作者信息 +

Establishment of doxorubicin induced cardiomyocyte injury model by human induced pluripotent stem cell-derived cardiomyocytes

CUI Ning¹ KE Bing-bing² WU Fu-jian³ BAI Rui³ LIU Tao-yan³ LI Lei¹ LAN Feng³CUI Ming ^1*

Author information +

文章历史 +

摘要

目的利用人诱导性多潜能干细胞来源的心肌细胞（hiPSC-CMs）技术，建立人源的阿霉素心肌细胞损伤模型。方法从人诱导性多潜能干细胞分化hiPSC-CMs，再用不同浓度阿霉素对hiPSC-CMs作用24 h后检测其细胞活性、钙瞬变、氧化应激和DNA损伤等表型。结果阿霉素诱导hiPSC-CMs细胞活力下降，破坏其钙瞬变，引起氧化应激水平上升，导致线粒体膜电位下降和造成DNA损伤，同时右丙亚胺对阿霉素心肌细胞损伤有保护作用。结论利用hiPSC-CMs成功建立了人源阿霉素心肌细胞损伤模型，克服了人心肌细胞难以获得及对药物反应存在种属差异的局限性，更好地用于阿霉素心脏毒性的机制研究及药物筛选。

Abstract

Objective To establish a humanized doxorubicin-induced cardiomyocyte injury model by using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Methods The human induced pluripotent stem cells were induced to differentiate into hiPSC-CMs. Then the phenotypes of hiPSC-CMs such including cell viability, calcium transients, oxidative stress and DNA damage were detected after treated with various concentrations of doxorubicin for 24 hours. Results Doxorubicin induced a decrease in cell viability of hiPSC-CMs, destroyed calcium transients, increasing oxidative stress, leading to decrease of mitochondrial membrane potential and causing DNA damage, meanwhile dexrazoxane had cardioprotective effects on hiPSC-CMs. Conclusion Doxorubicin induced cardiomyocyte injury model is successfully established with hiPSC-CMs, overcoming the limitation of difficult access to human cardiomyocytes and the different reaction to drug between species, so could to better study on the mechanism of doxorubicin-induced cardiotoxicity and drug screening.

导出引用

崔宁柯兵兵吴福建白蕊刘涛燕李蕾兰峰崔鸣. 阿霉素致人诱导性多潜能干细胞来源的心肌细胞损伤模型的建立[J]. 解剖学报. 2018, 49(3): 309-316 https://doi.org/10.16098/j.issn.0529-1356.2018.03.007

CUI Ning KE Bing-bing WU Fu-jian BAI Rui LIU Tao-yan LI Lei LAN Feng CUI Ming.

Establishment of doxorubicin induced cardiomyocyte injury model by human induced pluripotent stem cell-derived cardiomyocytes

[J]. Acta Anatomica Sinica. 2018, 49(3): 309-316 https://doi.org/10.16098/j.issn.0529-1356.2018.03.007

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