来自干细胞的心肌细胞表现出不律性潜在
Ying Ming Zhang1, Criss Hartzell, Michael Narlow
1Department of Medicine, Emory University, Atlanta, Ga 30033, USA.
Circulation
|September 5, 2002
概括
胚胎干细胞 (ESCs) 和胚胎癌细胞 (ECCs) 分化为心肌细胞表现出节律失调的特性,包括自发活动和触发的节律失调,警告不要在细胞治疗中使用它们.
科学领域:
- 心脏病学 心脏病学
- 干细胞生物学 干细胞生物学
- 电子生理学 电子生理学
背景情况:
- 从胚胎干细胞 (ESC) 和胚胎癌细胞 (ECC) 衍生出的心肌细胞 (CMs) 具有一些,但并非所有的成年肌细胞特征.
- 在受损的心肌中,ESC显示出植入的潜力,这表明对心肌病的治疗应用.
- 来自ESC和ECC的CM的节律失常性质需要进行彻底的研究.
研究的目的:
- 调查从小鼠ESC和ECC区分出的心肌细胞的节律失常性潜力.
- 描述这些衍生CM的电生理学特性,并确定这些衍生CM中的潜在心律失常机制.
主要方法:
- 整细胞补丁记录被用来研究心肌细胞在体外.
- 分析了动作潜能 (AP) 形态,上升速度 (dV/dt) 和AP持续时间.
- 使用药理剂和离子操纵来诱导和评估触发活动和后分极化.
主要成果:
- 衍生CMs表现出显著的AP形态异质性,最大dV/dt降低,AP持续时间延长.
- 在培养的CM中观察到自发的电活动和频繁的触发活动.
- 在各种条件下,包括药物刺激和离子变化,早期脱极化后 (EAD) 是可诱导的.
- 延迟后去极化 (DADs) 很容易被高血症或异二醇诱导.
结论:
- 来自ESC和ECC的CM分化为至少三个不同的AP表型.
- 这些CM表现出自发活动,dV/dt受损,AP持续时间延长,以及易于诱导的触发性心律失常.
- 这些发现需要谨慎使用ESC在细胞移植治疗中,因为它们有可能通过重新进入,自动性或触发活动诱导心律失常.
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