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个体化房颤治疗:干细胞和计算机疾病模型的作用。

Personalizing therapy for atrial fibrillation: the role of stem cell and in silico disease models.

机构信息

University of British Columbia, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada.

Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, ON, Canada.

出版信息

Cardiovasc Res. 2018 Jun 1;114(7):931-943. doi: 10.1093/cvr/cvy090.

Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with substantial morbidity. There is considerable inter-patient variability in the pathologic processes that promote AF, and this variability likely has a significant genetic basis. Clinically this is reflected by the observation that anti-arrhythmic drugs and interventional procedures have highly variable efficacy, and this highlights the need for adopting a more efficacious personalized approach. We explore recent advancements in both in silico and stem cell disease models that set the stage for a personalized approach. Specifically we highlight new mechanistic insights in AF; the future role of computational models in planning personalized ablation strategies; the potential role of stem cell models as a preclinical platform for drug development; and the potential to use gene-editing technology to create patient-specific stem cell models. Finally, we introduce the concept of integrating stem cell models with computational modelling to create a novel pipeline for patient-specific drug discovery and development.

摘要

心房颤动(AF)是最常见的心律失常,与大量发病率有关。促进 AF 的病理过程在患者之间存在相当大的可变性,这种可变性可能具有重要的遗传基础。临床上,这表现在抗心律失常药物和介入性手术的疗效高度可变,这突出了需要采用更有效的个性化方法。我们探讨了计算机模拟和干细胞疾病模型方面的最新进展,为个性化方法奠定了基础。具体来说,我们强调了 AF 的新机制见解;计算模型在规划个性化消融策略中的未来作用;干细胞模型作为药物开发临床前平台的潜在作用;以及使用基因编辑技术创建患者特异性干细胞模型的潜力。最后,我们介绍了将干细胞模型与计算模型集成以创建用于患者特异性药物发现和开发的新管道的概念。

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