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一种用于筛选干细胞治疗后心律失常事件的新型高通量方法。

A novel high throughput approach to screen for cardiac arrhythmic events following stem cell treatment.

作者信息

Tung William, Weintraub Neal L, Berman Adam E, Tang Yaoliang

机构信息

Vascular Biology Center, Department of Medicine, Medical College of Georgia/Georgia Regents University, 1459 Laney Walker Blvd, Augusta, GA 30912, USA.

Vascular Biology Center, Department of Medicine, Medical College of Georgia/Georgia Regents University, 1459 Laney Walker Blvd, Augusta, GA 30912, USA.

出版信息

Med Hypotheses. 2015 Apr;84(4):294-7. doi: 10.1016/j.mehy.2015.01.015. Epub 2015 Jan 19.

Abstract

Although stem cell therapy is promising for repairing damaged cardiac tissue and improving heart function, there are safety concerns, especially regarding the risk of arrhythmias, which can be life threatening. To address this issue, we propose to develop a novel screening system to evaluate arrhythmic risk associated with stem cell therapy using a high-throughput multielectrode array system that can measure conduction velocity and action potential duration in cardiomyocytes co-cultured with different types of stem cells, such as mesenchymal stem cells, skeletal myoblasts, and resident cardiac stem cells. We will assess the arrhythmic potential of each of these types of stem cells under normoxic and hypoxic conditions, with/without application of oxidative stress or catecholamines. We hypothesize that these methods will prove to be an effective way to screen for arrhythmic risk of cardiac stem cell therapy. Ultimately, our approach can potentially be personalized to develop a robust screening protocol in order to identify which stem cell type carries the least amount of risk for arrhythmia. This system will have great clinical benefit to improve the risk/benefit ratio of human stem cell therapy for heart disease.

摘要

尽管干细胞疗法在修复受损心脏组织和改善心脏功能方面前景广阔,但仍存在安全问题,尤其是心律失常的风险,这可能会危及生命。为了解决这个问题,我们提议开发一种新型筛选系统,使用高通量多电极阵列系统来评估与干细胞疗法相关的心律失常风险,该系统可以测量与不同类型干细胞(如间充质干细胞、骨骼肌成肌细胞和心脏驻留干细胞)共培养的心肌细胞的传导速度和动作电位持续时间。我们将评估在常氧和缺氧条件下,在施加/不施加氧化应激或儿茶酚胺的情况下,每种类型干细胞的心律失常可能性。我们假设这些方法将被证明是筛选心脏干细胞疗法心律失常风险的有效方法。最终,我们的方法有可能实现个性化,以制定一个强大的筛选方案,从而确定哪种干细胞类型发生心律失常的风险最小。该系统将对提高人类干细胞治疗心脏病的风险/效益比具有巨大的临床益处。

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Curr Opin Cardiol. 2013 Jan;28(1):36-42. doi: 10.1097/HCO.0b013e32835b0979.
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Metabolic stress, reactive oxygen species, and arrhythmia.代谢应激、活性氧和心律失常。
J Mol Cell Cardiol. 2012 Feb;52(2):454-63. doi: 10.1016/j.yjmcc.2011.09.018. Epub 2011 Sep 25.
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Cardiac cell therapy: lessons from clinical trials.心脏细胞治疗:临床试验的经验教训。
J Mol Cell Cardiol. 2011 Feb;50(2):258-65. doi: 10.1016/j.yjmcc.2010.06.010. Epub 2010 Jun 30.

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