与间充质干细胞共培养后,冬眠心肌细胞的线粒体呼吸能力恢复。

Cell medicine Pub Date : 2019-03-06 eCollection Date: 2019-01-01 DOI:10.1177/2155179019834938
Laura L Hocum Stone, Erin Chappuis, Maribel Marquez, Edward O McFalls, Rosemary F Kelly, Tammy Butterick
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引用次数: 0

摘要

冬眠心肌是缺血性心脏病的一个子集,其特征是有活力但功能失调的组织。冬眠心肌的标准治疗方法是冠状动脉旁路移植,它可以减少心律失常,提高存活率,但不能完全恢复功能,这在目前可用的治疗方法中存在差距。对冬眠心肌的大型动物研究表明,尽管进行了外科血运重建,但线粒体动力学受损是持续性心脏功能障碍的根本原因。本研究提出了一种新的冬眠心肌细胞体外模型,以研究冬眠心肌细胞的线粒体主动呼吸,并测试间充质干细胞对受损线粒体功能的旁分泌作用。心肌细胞暴露于1%氧气的缺氧条件下24小时,导致与冬眠心肌心脏组织一致的表型,包括高工作状态下的呼吸能力降低、线粒体蛋白表达降低和细胞活力保持。冬眠心肌细胞与间充质干细胞的共培养恢复了线粒体呼吸功能,可能是通过增加增殖物激活受体γ共激活因子1-α驱动的线粒体生物发生。用间充质干细胞共培养处理冬眠心肌心肌细胞显示出线粒体功能和ATP产生的改善,这两者对心脏组织的有效功能都至关重要。这些结果表明,间充质干细胞治疗作为血运重建的辅助治疗,可以解决目前冬眠心肌患者治疗的空白。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Mitochondrial Respiratory Capacity is Restored in Hibernating Cardiomyocytes Following Co-Culture with Mesenchymal Stem Cells.

Mitochondrial Respiratory Capacity is Restored in Hibernating Cardiomyocytes Following Co-Culture with Mesenchymal Stem Cells.

Mitochondrial Respiratory Capacity is Restored in Hibernating Cardiomyocytes Following Co-Culture with Mesenchymal Stem Cells.

Hibernating myocardium is a subset of ischemic cardiac disease characterized by viable but dysfunctional tissue. Standard treatment for hibernating myocardium is coronary artery bypass graft, which reduces arrhythmias and improves survival but does not fully restore function, presenting a gap in currently available treatments. Large animal studies of hibernating myocardium have identified impaired mitochondrial dynamics as a root cause of persistent cardiac dysfunction despite surgical revascularization. This study presents a novel in vitro model of hibernating myocardium cardiomyocytes to study active mitochondrial respiration in hibernating myocardium cells, and to test the paracrine effect of mesenchymal stem cells on impaired mitochondrial function. Exposure of cardiomyocytes to hypoxic conditions of 1% oxygen for 24 hours resulted in a phenotype consistent with hibernating myocardium cardiac tissue, including decreased respiratory capacity under high work states, decreased expression of mitochondrial proteins, and preserved cellular viability. Co-culture of hibernating myocardium cardiomyocytes with mesenchymal stem cells restored mitochondrial respiratory function, potentially via an increase in proliferator-activated receptor gamma coactivator 1-alpha-driven mitochondrial biogenesis. Co-culture treatment of hibernating myocardium cardiomyocytes with mesenchymal stem cells shows improvement in both mitochondrial function and ATP production, both of which are critical for effectively functioning cardiac tissue. These results suggest that mesenchymal stem cell therapy as an adjunct treatment to revascularization may address the current gap in treatment for hibernating myocardium patients.

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来源期刊
Cell medicine
Cell medicine MEDICINE, RESEARCH & EXPERIMENTAL-
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