Chauveau Samuel, Brink Peter R, Cohen Ira S
Department of Physiology and Biophysics, Institute for Molecular Cardiology, Stony Brook University, Stony Brook, NY, USA.
Department of Physiology and Biophysics, Institute for Molecular Cardiology, Stony Brook University, Stony Brook, NY, USA.
Cytotherapy. 2014 Jul;16(7):873-80. doi: 10.1016/j.jcyt.2014.02.014. Epub 2014 May 13.
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. However, 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: (i) mesenchymal stem cells used as a suitcase for delivering pacemaker genes and (ii) 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.
电子起搏器是治疗心动过缓相关症状的标准疗法，但存在缺点。在过去15年中，实验证据表明基于基因和细胞的疗法可以制造生物起搏器。最近，有报道称基于腺病毒的方法可实现生理上可接受的心率。然而，基于腺病毒的蛋白质表达持续时间不超过4周，这限制了其临床应用。基于细胞的平台是实现更长时间表达的潜在候选者。目前有两种基于细胞的方法正在进行测试：（i）间充质干细胞用作携带起搏器基因的载体；（ii）多能干细胞分化为具有内源性起搏器活性的心脏谱系细胞。本文综述了目前在构建生物起搏器方面取得的成果，确定了该设备适用的患者群体，并指出了在细胞疗法能够取代当前电子设备之前仍面临的挑战。
