首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Cardiomyocytes from phorbol myristate acetate-activated mesenchymal stem cells restore electromechanical function in infarcted rat hearts
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Cardiomyocytes from phorbol myristate acetate-activated mesenchymal stem cells restore electromechanical function in infarcted rat hearts

机译:佛波醇肉豆蔻酸酯乙酸酯激活的间充质干细胞的心肌细胞恢复梗死大鼠心脏的机电功能

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摘要

Despite the safety and feasibility of mesenchymal stem cell (MSC) therapy, an optimal cell type has not yet emerged in terms of electromechanical integration in infarcted myocardium. We found that poor to moderate survival benefits of MSC-implanted rats were caused by incomplete electromechanical integration induced by tissue heterogeneity between myocytes and engrafted MSCs in the infarcted myocardium. Here, we report the development of cardio-genic cells from rat MSCs activated by phorbol myristate acetate, a PKC activator, that exhibited high expressions of cardiac-specific markers and Ca~(2+) homeostasis-related proteins and showed adren-ergic receptor signaling by norepinephrine. Histological analysis showed high connexin 43 coupling, few inflammatory cells, and low fibrotic markers in myocardium implanted with these phorbol myristate acetate-activated MSCs. Infarct hearts implanted with these cells exhibited restoration of conduction velocity through decreased tissue heterogeneity and improved myocardial contractility. These findings have major implications for the development of better cell types for electromechanical integration of cell-based treatment for infarcted myocardium.
机译:尽管间充质干细胞(MSC)治疗的安全性和可行性,但就梗死心肌的机电整合而言,最佳细胞类型尚未出现。我们发现,植入MSC的大鼠存活能力差至中度是由于梗死心肌中心肌细胞和植入的MSC之间组织异质性引起的不完全机电整合所致。在此,我们报道了由佛波肉豆蔻酸酯乙酸酯(一种PKC激活剂)激活的大鼠MSCs的心脏细胞的发育,该细胞表现出高表达的心脏特异性标志物和Ca〜(2+)稳态相关蛋白,并表现出肾上腺能受体去甲肾上腺素的信号。组织学分析显示,在植入这些佛波醇肉豆蔻酸酯乙酸酯激活的MSC的心肌中,高连接蛋白43偶联,少量炎症细胞和低纤维化标记物。植入这些细胞的梗塞心脏通过降低组织异质性和改善心肌收缩力,恢复了传导速度。这些发现对开发更好的细胞类型以进行基于心肌梗塞的细胞治疗的机电整合具有重大意义。

著录项

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  • 作者单位

    Research Institute of Science for Aging, Yonsei University, Seoul 120-752, Korea;

    Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea;

    Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea;

    Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea,Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea;

    Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea,Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea;

    Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea,Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea;

    Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea;

    Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea,Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea;

    Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea,Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea;

    Department of Integrated Omics for Biomedical Sciences, Graduate School, Yonsei University, Seoul 120-749, Korea;

    Department of Integrated Omics for Biomedical Sciences, Graduate School, Yonsei University, Seoul 120-749, Korea;

    Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea,Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea;

    Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea,Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 120-752, Korea;

    Department of Electrical and Electronic Engineering, Yonsei University, Seoul 120-749, Korea;

    Department of Electrical and Electronic Engineering, Yonsei University, Seoul 120-749, Korea;

    Cardiology Division, Yonsei University College of Medicine, Seoul 120-752,Korea;

    Department of Integrated Omics for Biomedical Sciences, Graduate School, Yonsei University, Seoul 120-749, Korea,Department of Chemistry, University of California, Berkeley, CA 94702;

    Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea,Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea,Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 120-752, Korea,Cardiology Division, Yonsei University College of Medicine, Seoul 120-752,Korea;

    Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea,Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea,Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 120-752, Korea;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    cell therapy; optical mapping; differentiation; heart infarction; arrhythmia;

    机译:细胞疗法;光学成像;分化;心肌梗塞;心律不齐;

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