Stem cell-based biological pacemakers from proof of principle to therapy: a review.

Stem cell-based biological pacemakers from proof of principle to therapy: a review.
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DOI:
10.1016/j.jcyt.2014.02.014
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发表时间:
2014-07
期刊:
影响因子:
4.5
通讯作者:
Cohen, Ira S.
Cohen, Ira S.
中科院分区:
医学3区
文献类型:
--
作者:
Chauveau, Samuel;Brink, Peter R.;Cohen, Ira S.

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电子起搏器是心动过缓相关症状的标准疗法,但也有缺点。在过去的15年里,实验证据已经证明,基于基因和细胞的疗法可以创造一个生物起搏器。最近,已经报道了基于腺病毒的方法的生理上可接受的速率。但腺病毒表达的蛋白质持续时间不超过4周,这限制了其临床应用。基于细胞的平台是更长表达的潜在候选者。目前有两种基于细胞的方法正在测试中:1)间充质干细胞用作递送起搏器基因的手提箱和2)多能干细胞分化为具有内源性起搏器活性的心脏谱系。本综述研究了目前在生物起搏器工程方面取得的成就,定义了该设备有用的患者人群,并确定了在细胞疗法取代当前电子设备之前仍然面临的挑战。
Electronic pacemakers are the standard therapy for bradycardia related symptoms but have shortcomings. Over the past 15 years experimental evidence has demonstrated that gene and cell-based therapies can create a biological pacemaker. Recently, physiologically acceptable rates have been reported with an adenovirus-based approach. But adenovirus-based protein expression does not last more than 4 weeks, which limits its clinical applicability. Cell-based platforms are potential candidates for longer expression. Currently there are two cell based approaches being tested: 1) Mesenchymal stem cells used as a suitcase for delivering pacemaker genes and 2) Pluripotent stem cells differentiated down a cardiac lineage with endogenous pacemaker activity. This review examines the current achievements in engineering a biological pacemaker, defines the patient population for whom this device would be useful and identifies the challenges still ahead before cell therapy can replace current electronic devices.
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