• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

开发高通量成像方法检测人多能干细胞来源心肌细胞中的细胞死亡。

Development of high content imaging methods for cell death detection in human pluripotent stem cell-derived cardiomyocytes.

机构信息

National Heart and Lung Institute, Imperial College, ICTEM, Hammersmith Campus, Du Cane Rd., London, UK.

出版信息

J Cardiovasc Transl Res. 2012 Oct;5(5):593-604. doi: 10.1007/s12265-012-9396-1. Epub 2012 Aug 16.

DOI:10.1007/s12265-012-9396-1
PMID:22896035
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3447146/
Abstract

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CM) are being investigated as a new source of cardiac cells for drug safety assessment. We developed a novel scalable high content microscopy-based method for the detection of cell death in hPSC-CM that can serve for future predictive in vitro cardio-toxicological screens. Using rat neonatal ventricular cardiomyocytes (RVNC) or hPSC-CM, assays for nuclear remodelling, mitochondrial status, apoptosis and necrosis were designed using a combination of fluorescent dyes and antibodies on an automated microscopy platform. This allowed the observation of a chelerythrine-induced concentration-dependent apoptosis to necrosis switch and time-dependent progression of early apoptotic cells towards a necrotic-like phenotype. Susceptibility of hPSC-CM to chelerythrine-stimulated apoptosis varied with time after differentiation, but at most time points, hPSC-CM were more resistant than RVNC. This simple and scalable humanized high-content assay generates accurate cardiotoxicity profiles that can serve as a base for further assessment of cardioprotective strategies and drug safety.

摘要

人多能干细胞衍生的心肌细胞（hPSC-CM）正在被研究作为一种新的心脏细胞来源，用于药物安全性评估。我们开发了一种新型的可扩展的基于高通量显微镜的方法，用于检测 hPSC-CM 中的细胞死亡，可用于未来的预测性体外心脏毒性筛选。使用大鼠新生心室心肌细胞（RVNC）或 hPSC-CM，通过在自动化显微镜平台上使用荧光染料和抗体的组合，设计了用于核重塑、线粒体状态、细胞凋亡和坏死的检测。这使得可以观察到石蒜碱诱导的浓度依赖性细胞凋亡向坏死的转变，以及早期凋亡细胞向坏死样表型的时间依赖性进展。hPSC-CM 对石蒜碱刺激的细胞凋亡的敏感性随分化后的时间而变化，但在大多数时间点，hPSC-CM 比 RVNC 更具抗性。这种简单且可扩展的人源化高通量测定法可生成准确的心脏毒性特征，可作为进一步评估心脏保护策略和药物安全性的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/3447146/acc5b0a6cc13/12265_2012_9396_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/3447146/e603aab4381e/12265_2012_9396_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/3447146/d2776a777c91/12265_2012_9396_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/3447146/93ccd3f4be7d/12265_2012_9396_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/3447146/68496628f4af/12265_2012_9396_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/3447146/0460c77245fe/12265_2012_9396_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/3447146/9617a3f3ac77/12265_2012_9396_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/3447146/acc5b0a6cc13/12265_2012_9396_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/3447146/e603aab4381e/12265_2012_9396_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/3447146/d2776a777c91/12265_2012_9396_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/3447146/93ccd3f4be7d/12265_2012_9396_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/3447146/68496628f4af/12265_2012_9396_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/3447146/0460c77245fe/12265_2012_9396_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/3447146/9617a3f3ac77/12265_2012_9396_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/3447146/acc5b0a6cc13/12265_2012_9396_Fig7_HTML.jpg

相似文献

1
Development of high content imaging methods for cell death detection in human pluripotent stem cell-derived cardiomyocytes.开发高通量成像方法检测人多能干细胞来源心肌细胞中的细胞死亡。
J Cardiovasc Transl Res. 2012 Oct;5(5):593-604. doi: 10.1007/s12265-012-9396-1. Epub 2012 Aug 16.
2
GATA4-targeted compound exhibits cardioprotective actions against doxorubicin-induced toxicity in vitro and in vivo: establishment of a chronic cardiotoxicity model using human iPSC-derived cardiomyocytes.GATA4 靶向化合物在体外和体内显示出对抗阿霉素诱导的毒性的心脏保护作用：用人诱导多能干细胞衍生的心肌细胞建立慢性心脏毒性模型。
Arch Toxicol. 2020 Jun;94(6):2113-2130. doi: 10.1007/s00204-020-02711-8. Epub 2020 Mar 17.
3
Cardiomyocytes from human pluripotent stem cells: From laboratory curiosity to industrial biomedical platform.源自人类多能干细胞的心肌细胞：从实验室的新奇事物到工业生物医学平台。
Biochim Biophys Acta. 2016 Jul;1863(7 Pt B):1728-48. doi: 10.1016/j.bbamcr.2015.10.014. Epub 2015 Oct 31.
4
Doxorubicin triggers bioenergetic failure and p53 activation in mouse stem cell-derived cardiomyocytes.多柔比星在小鼠干细胞来源的心肌细胞中引发生物能量衰竭和 p53 激活。
Toxicol Appl Pharmacol. 2018 Jun 1;348:1-13. doi: 10.1016/j.taap.2018.04.009. Epub 2018 Apr 11.
5
Metabolic Maturation of Human Pluripotent Stem Cell-Derived Cardiomyocytes by Inhibition of HIF1α and LDHA.通过抑制 HIF1α 和 LDHA 实现人多能干细胞源性心肌细胞的代谢成熟
Circ Res. 2018 Oct 12;123(9):1066-1079. doi: 10.1161/CIRCRESAHA.118.313249.
6
High-throughput drug profiling with voltage- and calcium-sensitive fluorescent probes in human iPSC-derived cardiomyocytes.高通量药物分析用人诱导多能干细胞源性心肌细胞中的电压和钙敏荧光探针。
Am J Physiol Heart Circ Physiol. 2016 Jul 1;311(1):H44-53. doi: 10.1152/ajpheart.00793.2015. Epub 2016 May 3.
7
The Use of Ratiometric Fluorescence Measurements of the Voltage Sensitive Dye Di-4-ANEPPS to Examine Action Potential Characteristics and Drug Effects on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.利用电压敏感染料Di-4-ANEPPS的比率荧光测量来检测人类诱导多能干细胞衍生心肌细胞的动作电位特征和药物作用。
Toxicol Sci. 2016 Dec;154(2):320-331. doi: 10.1093/toxsci/kfw171. Epub 2016 Sep 11.
8
High-throughput cardiac safety evaluation and multi-parameter arrhythmia profiling of cardiomyocytes using microelectrode arrays.使用微电极阵列对心肌细胞进行高通量心脏安全性评估和多参数心律失常分析。
Toxicol Appl Pharmacol. 2015 Oct 15;288(2):249-57. doi: 10.1016/j.taap.2015.07.024. Epub 2015 Jul 29.
9
Structural and functional screening in human induced-pluripotent stem cell-derived cardiomyocytes accurately identifies cardiotoxicity of multiple drug types.在人诱导多能干细胞衍生的心肌细胞中进行的结构和功能筛选能够准确识别多种药物类型的心脏毒性。
Toxicol Appl Pharmacol. 2015 May 15;285(1):51-60. doi: 10.1016/j.taap.2015.03.008. Epub 2015 Apr 2.
10
Probing flecainide block of I using human pluripotent stem cell-derived ventricular cardiomyocytes adapted to automated patch-clamping and 2D monolayers.应用自动化膜片钳和 2D 单层技术，用人多能干细胞来源的心室肌细胞探测氟卡尼对 I 电流的阻断作用。
Toxicol Lett. 2018 Sep 15;294:61-72. doi: 10.1016/j.toxlet.2018.05.006. Epub 2018 May 21.

引用本文的文献

1
Human Stem Cells for Cardiac Disease Modeling and Preclinical and Clinical Applications-Are We on the Road to Success?人类干细胞在心脏疾病建模及临床前和临床应用中的作用——我们是否正在走向成功？
Cells. 2023 Jun 27;12(13):1727. doi: 10.3390/cells12131727.
2
Cardiac stem cells: Current knowledge and future prospects.心脏干细胞：当前认知与未来展望。
World J Stem Cells. 2022 Jan 26;14(1):1-40. doi: 10.4252/wjsc.v14.i1.1.
3
Risk Compounds, Preclinical Toxicity Evaluation, and Potential Mechanisms of Chinese Materia Medica-Induced Cardiotoxicity.

本文引用的文献

1
Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy.家族性扩张型心肌病的患者特异性诱导多能干细胞模型。
Sci Transl Med. 2012 Apr 18;4(130):130ra47. doi: 10.1126/scitranslmed.3003552.
2
Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome.利用 iPSC 衍生神经元揭示与 Timothy 综合征相关的细胞表型。
Nat Med. 2011 Nov 27;17(12):1657-62. doi: 10.1038/nm.2576.
3
Model for long QT syndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture.
中药致心脏毒性的风险化合物、临床前毒性评估及潜在机制
Front Pharmacol. 2021 Mar 30;12:578796. doi: 10.3389/fphar.2021.578796. eCollection 2021.
4
A protocol for metabolic characterization of human induced pluripotent stem cell-derived cardiomyocytes (iPS-CM).一项关于人诱导多能干细胞衍生心肌细胞（iPS-CM）代谢特征分析的方案。
MethodsX. 2019 May 29;7:100572. doi: 10.1016/j.mex.2019.05.028. eCollection 2020.
5
Review of high-content screening applications in toxicology.毒理学中高通量筛选应用的回顾。
Arch Toxicol. 2019 Dec;93(12):3387-3396. doi: 10.1007/s00204-019-02593-5. Epub 2019 Oct 29.
6
Stem cell models as an model for predictive toxicology.干细胞模型作为预测毒理学的模型。
Biochem J. 2019 Apr 15;476(7):1149-1158. doi: 10.1042/BCJ20170780.
7
Muscle-specific stress fibers give rise to sarcomeres in cardiomyocytes.肌节特异性应激纤维在心肌细胞中产生。
Elife. 2018 Dec 12;7:e42144. doi: 10.7554/eLife.42144.
8
Stem cells are the most sensitive screening tool to identify toxicity of GATA4-targeted novel small-molecule compounds.干细胞是鉴定 GATA4 靶向新型小分子化合物毒性的最敏感筛选工具。
Arch Toxicol. 2018 Sep;92(9):2897-2911. doi: 10.1007/s00204-018-2257-1. Epub 2018 Jul 9.
9
Development of In Vitro Drug-Induced Cardiotoxicity Assay by Using Three-Dimensional Cardiac Tissues Derived from Human Induced Pluripotent Stem Cells.利用源自人诱导多能干细胞的三维心脏组织开发体外药物诱导的心脏毒性检测方法。
Tissue Eng Part C Methods. 2018 Jan;24(1):56-67. doi: 10.1089/ten.TEC.2017.0247. Epub 2017 Nov 17.
10
Can Human Pluripotent Stem Cell-Derived Cardiomyocytes Advance Understanding of Muscular Dystrophies?人多能干细胞衍生的心肌细胞能否促进对肌肉疾病的理解？
J Neuromuscul Dis. 2016 Aug 30;3(3):309-332. doi: 10.3233/JND-150133.
利用人类诱导多能干细胞建立长 QT 综合征 2 型模型，在细胞培养中显示出心律失常特征。
Dis Model Mech. 2012 Mar;5(2):220-30. doi: 10.1242/dmm.008409. Epub 2011 Nov 3.
4
A protective antiarrhythmic role of ursodeoxycholic acid in an in vitro rat model of the cholestatic fetal heart.熊去氧胆酸在胆汁淤积胎儿心脏体外大鼠模型中的保护抗心律失常作用。
Hepatology. 2011 Oct;54(4):1282-92. doi: 10.1002/hep.24492. Epub 2011 Aug 1.
5
Drug evaluation in cardiomyocytes derived from human induced pluripotent stem cells carrying a long QT syndrome type 2 mutation.携长 QT 综合征 2 型突变的人诱导多能干细胞衍生的心肌细胞中的药物评估。
Eur Heart J. 2011 Apr;32(8):952-62. doi: 10.1093/eurheartj/ehr073. Epub 2011 Mar 2.
6
Modulation of human embryonic stem cell-derived cardiomyocyte growth: a testbed for studying human cardiac hypertrophy?人胚胎干细胞源性心肌细胞生长的调控：研究人类心肌肥厚的试验平台？
J Mol Cell Cardiol. 2011 Feb;50(2):367-76. doi: 10.1016/j.yjmcc.2010.10.029. Epub 2010 Nov 1.
7
Patient-specific induced pluripotent stem-cell models for long-QT syndrome.长 QT 综合征的患者特异性诱导多能干细胞模型。
N Engl J Med. 2010 Oct 7;363(15):1397-409. doi: 10.1056/NEJMoa0908679. Epub 2010 Jul 21.
8
Nucleoside drugs induce cellular differentiation by caspase-dependent degradation of stem cell factors.核苷类药物通过半胱天冬酶依赖性降解干细胞因子诱导细胞分化。
PLoS One. 2010 May 19;5(5):e10726. doi: 10.1371/journal.pone.0010726.
9
Caspase 3/caspase-activated DNase promote cell differentiation by inducing DNA strand breaks.半胱天冬酶 3/半胱天冬酶激活的 DNA 酶通过诱导 DNA 链断裂促进细胞分化。
Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4230-5. doi: 10.1073/pnas.0913089107. Epub 2010 Feb 16.
10
Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features.细胞程序性坏死、细胞坏死和继发性坏死具有相似的细胞解体特征。
Cell Death Differ. 2010 Jun;17(6):922-30. doi: 10.1038/cdd.2009.184. Epub 2009 Dec 11.