...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Frontiers in Physiology >A Hybrid Model for Safety Pharmacology on an Automated Patch Clamp Platform: Using Dynamic Clamp to Join iPSC-Derived Cardiomyocytes and Simulations of I k1 Ion Channels in Real-Time
【24h】

A Hybrid Model for Safety Pharmacology on an Automated Patch Clamp Platform: Using Dynamic Clamp to Join iPSC-Derived Cardiomyocytes and Simulations of I k1 Ion Channels in Real-Time

机译：自动化膜片钳平台上安全药理学的混合模型：使用动态钳子连接iPSC衍生的心肌细胞和I k1 离子通道的实时模拟

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

An important aspect of the Comprehensive In Vitro Proarrhythmia Assay (CiPA) proposal is the use of human stem cell-derived cardiomyocytes and the confirmation of their predictive power in drug safety assays. The benefits of this cell source are clear; drugs can be tested in vitro on human cardiomyocytes, with patient-specific genotypes if needed, and differentiation efficiencies are generally excellent, resulting in a virtually limitless supply of cardiomyocytes. There are, however, several challenges that will have to be surmounted before successful establishment of hSC-CMs as an all-round predictive model for drug safety assays. An important factor is the relative electrophysiological immaturity of hSC-CMs, which limits arrhythmic responses to unsafe drugs that are pro-arrhythmic in humans. Potentially, immaturity may be improved functionally by creation of hybrid models, in which the dynamic clamp technique joins simulations of lacking cardiac ion channels (e.g., I_(K1)) with hSC-CMs in real-time during patch clamp experiments. This approach has been used successfully in manual patch clamp experiments, but throughput is low. In this study, we combined dynamic clamp with automated patch clamp of iPSC-CMs in current clamp mode, and demonstrate that I_(K1) conductance can be added to iPSC-CMs on an automated patch clamp platform, resulting in an improved electrophysiological maturity.
机译：综合体外心律失常分析（CiPA）提议的一个重要方面是使用人类干细胞衍生的心肌细胞并在药物安全性分析中确认其预测能力。这种细胞来源的好处显而易见。可以在人类心肌细胞上对药物进行体外测试，如果需要的话，可以使用患者特定的基因型，而且分化效率通常非常好，从而导致了几乎无限量的心肌细胞供应。然而，在成功建立hSC-CM作为药物安全性检测的全面预测模型之前，还必须克服几个挑战。一个重要因素是hSC-CM的相对电生理不成熟，这限制了人们对不安全药物的心律失常反应，而这种药物在人体内是促心律失常的。潜在地，通过创建混合模型可以在功能上改善不成熟度，在该模型中，动态钳位技术将贴片钳位实验中实时的缺少心脏离子通道（例如I_（K1））的模拟与hSC-CM结合在一起。该方法已成功用于手动膜片钳实验，但通量较低。在这项研究中，我们将动态钳位与iPSC-CM的自动膜片钳在电流钳模式下结合使用，并证明可以在自动膜片钳平台上将I_（K1）电导添加到iPSC-CM，从而提高了电生理成熟度。

著录项

相似文献

  • 外文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号