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Mesenchymal stem cells neither fully acquire the electrophysiological properties of mature cardiomyocytes nor promote ventricular arrhythmias in infarcted rats

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Abstract

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 Ca2+ current during their survival. When induced by Ca2+, 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.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No: 30800455, 81000063) and Research Fund for the Doctoral Program of Higher Education of China (No: 200806981027). We thank Prof. Zhiquan Liu and Dr. Min Gong for their helpful suggestions in study design.

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  1. Department of Cardiovascular Medicine, First Affiliated Hospital of the Xi’an Jiaotong University School of Medicine, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an, Shaanxi, 710061, People’s Republic of China

    Feng Wei, Ting-Zhong Wang, Jing Zhang, Zu-Yi Yuan, Hong-Yan Tian, Ya-Juan Ni, Xiao-Zhen Zhuo, Ke Han, Yu Liu, Qun Lu, Hong-Yuan Bai & Ai-Qun Ma

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F. Wei and T.-Z. Wang contributed equally to the work.

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Wei, F., Wang, TZ., Zhang, J. et al. Mesenchymal stem cells neither fully acquire the electrophysiological properties of mature cardiomyocytes nor promote ventricular arrhythmias in infarcted rats. Basic Res Cardiol 107, 274 (2012). https://doi.org/10.1007/s00395-012-0274-4

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