Arrhythmia in stem cell transplantation.
Arrhythmia in stem cell transplantation.
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DOI：
10.1016/j.ccep.2015.03.012
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发表时间：
2015-06
影响因子：
--
通讯作者：
Ardehali R
中科院分区：
文献类型：
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作者：
Almeida SO;Skelton RJ;Adigopula S;Ardehali R
干细胞再生疗法有望在整个医学领域治疗疾病。最近的临床试验已经证实了干细胞输送到心脏的安全性，结果有希望，但结果不一。虽然在临床前阶段已经取得了重大进展，但心脏细胞疗法的临床应用受到技术挑战的限制，包括无法分离能够稳健植入和再生的心脏特异性祖细胞的纯群体，缺乏适当的临床前动物模型，最佳递送模式的不确定性，缺乏足够的成像模式，以及缺乏对移植细胞命运的了解。移植细胞不能在结构和功能上整合到宿主心肌中可能对患者造成致瘤风险。这部分取决于移植细胞的类型，其中间隙连接如连接蛋白-43的表达不仅对机电整合至关重要，而且已发现其对移植后的电不稳定性具有保护作用。此外，某些细胞递送方法，如心肌内注射，具有更高的心律失常率。细胞移植的促炎性的其他潜在因素包括由于移植物和宿主之间的传导速度的异质性以及移植物自律性而导致的折返途径。在本文中，我们讨论了细胞递送到心脏的致瘤潜力。
Stem cell regenerative therapies hold promise for treating diseases across the spectrum of medicine. Recent clinical trials have confirmed the safety of stem cell delivery to the heart with promising but variable results. While significant progress has been made in the preclinical stages, the clinical application of cardiac cell therapy is limited by technical challenges, including inability to isolate a pure population of cardiac-specific progenitors capable of robust engraftment and regeneration, lack of appropriate pre-clinical animal models, uncertainty about the best mode of delivery, paucity of adequate imaging modalities, and lack of knowledge about the fate of transplanted cells. The inability of transplanted cells to structurally and functionally integrate into the host myocardium may pose arrhythmogenic risk to patients. This is in part dependent on the type of cell transplanted, where the expression of gap junctions such as connexin-43 is essential not only for electromechanical integration, but has also been found to be protective against electrical instability post-transplant. Additionally, certain methods of cell delivery, such as intramyocardial injection, carry a higher rate of arrhythmias. Other potential contributors to the arrhythmogenicity of cell transplantation include re-entrant pathways due to heterogeneity in conduction velocities between graft and host as well as graft automaticity. In this paper, we discuss the arrhythmogenic potential of cell delivery to the heart.