使用人类诱导的多能干细胞干细胞衍生的心肌细胞和低阻抗微电极阵列查药物诱导的心律失常[纠正]
Enrique G Navarrete1, Ping Liang, Feng Lan
1Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA (E.G.N., P.L., F.L., V.S.-F., T.G., A.S., P.W.B., A.S.L., H.W., S.M.W., J.C.W.); Institute for Stem Cell Biology and Regenerative Medicine, Stanford, CA (E.G.N., P.L., F.L., V.S.-F., T.G., A.S., P.W.B., A.S.L., H.W., S.M.W.); Stanford Cardiovascular Institute, Stanford, CA (E.G.N., P.L., F.L., V.S.-F., C.S., T.G., P.W.B., B.P., A.S.L., H.W., R.E.B., S.M.W., R.C.R., J.C.W.); Department of Radiology, Stanford, CA (E.G.N., P.L., F.L., V.S.-F., T.G., P.W.B., A.S.L., H.W., J.C.W.); School of Mechanical Engineering, Stanford, CA (C.S.); Department of Cardiothoracic Surgery, Stanford, CA (B.P., R.E.B., R.C.R.); Department of Pharmacology, University of California, Davis, CA (D.M.B.).
人类诱导的多能干细胞衍生心肌细胞 (hiPSC-CMs) 使用微电极阵列 (MEA) 系统有效选药物诱导的心律失常,为当前的方法提供了优越的替代方案.
科学领域:
- 心血管药理学心血管药理学
- 干细胞生物学 干细胞生物学
- 药物开发 药物开发
背景情况:
- 药物诱导的心律失常是药物开发失败的主要原因之一.
- 目前的临床前心脏毒性查方法有局限性.
- 人类诱导的多能干细胞衍生心肌细胞 (hiPSC-CMs) 具有与原始细胞的功能相似性和可扩展性.
研究的目的:
- 为了评估hiPSC-CMs与低阻抗微电极阵列 (MEA) 系统相结合,用于临床前心脏毒性查.
- 改进行业标准的药物诱导性心律失常查.
- 为了确定药物效应和心律失常的潜在危险因素.
主要方法:
- 使用低阻抗MEA系统评估hiPSC-CMs的药理反应.
- 测试了一组具有良好的特征的药物,包括已知的hERG抑制剂.
- 在诱导后65-95天,对跳动胚胎体的反应进行了监测.
主要成果:
- hiPSC-CMs准确地回顾了已知的药物效应,包括对hERG抑制剂的torsadogenic反应,如sotalol和quinidine.
- 在MEA/hiPSC-CM试验中,正确识别了假阴性和假阳性hERG抑制剂.
- 在药物治疗的hiPSC-CM中观察到早期的脱极化和宫外心跳,与临床和动物模型发现一致.
结论:
- 药物诱导的心律失常可以在使用MEA的hiPSC-CM中可靠地复制和记录.
- MEA/hiPSC-CM测定是一种敏感,强大和高效的药物有效性和心律失常查平台.
- 这种系统显示了降低药物开发成本的潜力,并比传统的细胞系和动物模型提供了优势.
更多相关视频
10:30Technical Applications of Microelectrode Array and Patch Clamp Recordings on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Published on: August 4, 2022
08:39Single-Cell Optical Action Potential Measurement in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Published on: December 22, 2020
相关概念视频
ECG Interpretation of Arrhythmias II: Atrial, Junctional and Ventricular Arrhythmias
Induced Pluripotent Stem Cells
Induced Pluripotent Stem Cells
Somatic...
Embryonic Stem Cells
ECG Interpretation of Arrhythmias I: Sinus Arrhythmias
Types of Arrhythmias
Sinus Node Arrhythmias
Sinus Bradycardia: Originating from the sinoatrial (SA) node, sinus bradycardia involves slower impulses, resulting in a heart rate of less than 60 beats per minute (bpm). Causes include sleep, vagal stimulation, beta-blockers, hypothyroidism,...
Induced-fit Model
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical...
