Implementing Biological Pacemakers: Design Criteria for Successful.
Implementing Biological Pacemakers: Design Criteria for Successful.
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DOI：
10.1161/circep.121.009957
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Ogle BM
中科院分区：
文献类型：
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作者：
Komosa ER;Wolfson DW;Bressan M;Cho HC;Ogle BM
将血液泵入全身的每一次心跳都是由窦房结（SAN）产生的电脉冲引起的。然而，许多疾病条件可阻碍SAN起搏器细胞产生一致动作电位和/或维持有序传导路径的能力，从而导致心律失常。对于有症状的患者，目前的治疗依赖于植入电子起搏装置。然而，留置硬体固有的并发症使得部分人群暂停使用器械治疗，包括儿科患者或有临时起搏需求的患者。基于细胞的生物起搏器，在体外或原位衍生，可以作为目前电子起搏器的治疗替代品。了解生物起搏器如何达到SAN的标准将有助于定义和展示其相对于当前治疗的优势。在这篇综述中，我们讨论了最近制造生物起搏器的方法，并描述了基于SAN基础生物学见解的设计标准，以指导未来的进展。我们强调需要通过维持相关蛋白、源库平衡、反映原生SAN微环境的生态位和变时能力来维持体内的长期疗效。以这些标准为重点，结合针对疾病适应症量身定制的交付方法，就可以实现临床实施。
Each heartbeat that pumps blood throughout the body is initiated by an electrical impulse generated in the sinoatrial node (SAN). However, a number of disease conditions can hamper the ability of the SAN’s pacemaker cells to generate consistent action potentials and/or maintain an orderly conduction path, leading to arrhythmias. For symptomatic patients, current treatments rely on implantation of an electronic pacing device. However, complications inherent to the indwelling hardware give pause to categorical use of device therapy for a subset of populations, including pediatric patients or those with temporary pacing needs. Cellular-based biological pacemakers, derived in vitro or in situ, could function as a therapeutic alternative to current electronic pacemakers. Understanding how biological pacemakers measure up to the SAN would facilitate defining and demonstrating its advantages over current treatments. In this review, we discuss recent approaches to creating biological pacemakers and delineate design criteria to guide future progress based on insights from basic biology of the SAN. We emphasize the need for long-term efficacy in vivo via maintenance of relevant proteins, source-sink balance, a niche reflective of the native SAN microenvironment, and chronotropic competence. With a focus on such criteria, combined with delivery methods tailored for disease indications, clinical implementation will be attainable.