Department of Cardiovascular Medicine, First Affiliated Hospital of the Xi'an Jiaotong University School of Medicine, Shaanxi, 710061, People's Republic of China.
Basic Res Cardiol. 2012 Jul;107(4):274. doi: 10.1007/s00395-012-0274-4. Epub 2012 Jun 29.
Electrophysiological properties of implanted mesenchymal stem cells (MSCs) in infarcted hearts remain unclear, and their proarrhythmic effect is still controversial. The intent of this study was to investigate electrophysiological properties and proarrhythmic effects of MSCs in infarcted hearts. Rats were randomly divided into a myocardial infarction (MI) group, a MI-DMEM group (received DMEM medium injection) and MI-MSCs group (received MSCs injection). Survival analysis showed that the majority of engrafted MSCs died at day 9 after transplantation. Engrafted MSCs expressed cardiac markers (MYH, cTnI, Cx43), cardiac ion channel genes (Kv1.4, Kv4.2 and Kir2.1) and potassium currents (I (to), I (K1) and I (KDR)), but did not express Nav1.5, Cav1.2, Na(+) current and Ca(2+) current during their survival. When induced by Ca(2+), implanted MSCs exhibited no contraction ability after being isolated from the heart. Following 8-week electrocardiography monitoring, the cumulative occurrence of ventricular arrhythmias (VAs) was not different among the three groups. However, the prolonged QRS duration in infarcted rats without VAs was significantly decreased in the MI-MSCs group compared with the other two groups. The inducibility of VAs in the MI-MSCs group was much lower than that in the MI and MI-DMEM groups (41.20 vs. 86.67 % and 92.86 %; P < 0.0125). The ventricular effective refractory period in MI-MSCs group was prolonged in comparison with that in the MI and MI-DMEM groups (56.0 ± 8.8 vs. 47.7 ± 8.8 ms and 45.7 ± 6.2 ms; P < 0.01). These results demonstrate that MSCs do not acquire the electrophysiological properties of mature cardiomyocytes during the survival period in the infarcted hearts. However, they can alleviate the electrical vulnerability and do not promote ventricular arrhythmias.
植入梗死心脏的间充质干细胞（MSCs）的电生理特性尚不清楚，其致心律失常作用仍存在争议。本研究旨在探讨梗死心脏中 MSCs 的电生理特性和致心律失常作用。大鼠随机分为心肌梗死（MI）组、MI-DMEM 组（注射 DMEM 培养基）和 MI-MSCs 组（注射 MSCs）。生存分析显示，大多数植入的 MSCs 在移植后第 9 天死亡。植入的 MSCs 表达心脏标志物（MYH、cTnI、Cx43）、心脏离子通道基因（Kv1.4、Kv4.2 和 Kir2.1）和钾电流（I(to)、I(K1) 和 I(KDR))，但在存活期间不表达 Nav1.5、Cav1.2、Na(+)电流和 Ca(2+)电流。当用 Ca(2+)诱导时，从心脏分离出的植入 MSCs 没有收缩能力。在 8 周心电图监测后，三组的室性心律失常（VAs）总发生率无差异。然而，与其他两组相比，无 VA 的梗死大鼠的 QRS 持续时间明显缩短。MI-MSCs 组的 VA 可诱导性明显低于 MI 和 MI-DMEM 组（41.20%比 86.67%和 92.86%；P<0.0125）。与 MI 和 MI-DMEM 组相比，MI-MSCs 组的心室有效不应期延长（56.0±8.8 比 47.7±8.8 和 45.7±6.2 ms；P<0.01）。这些结果表明，在梗死心脏中，MSCs 在存活期间不会获得成熟心肌细胞的电生理特性。然而，它们可以减轻电脆弱性，并不促进室性心律失常。
