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首页> 外文期刊>Cell and Tissue Research >Cardiomyogenesis of periodontal ligament-derived stem cells by dynamic tensile strain
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Cardiomyogenesis of periodontal ligament-derived stem cells by dynamic tensile strain

机译：通过动态拉伸应变实现牙周韧带干细胞的心脏肌生成

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Cellular therapies for the treatment of myocardial infarction have proven to be an invaluable tool in recent years and provide encouraging evidence for the possibility to restore normal heart function. However, questions still remain as to the optimal cell source, pre-conditioning methods and delivery techniques for such an application. This study explores the use of a population of stem cells arising from the neural crest and isolated from adult human periodontal ligament along with short-term mechanical strain as an inducer of cardiomyogenesis and possibly pre-conditioning stimulus for cellular cardiomyoplasty. Cells were subjected to a short-term dynamic mechanical tension in our custom-built bioreactor and analyzed for cardiomyogenic commitment. Mechanical strain elicited a cardiomyogenic response from the cells following just 2 h of stimulation. Mechanical strain activated and translocated cardiac-specific transcription factors GATA4, MEF2C and Nkx2.5, and induced expression of the sarcomeric actin and cardiac troponin T proteins. Mechanical strain induced production of significantly higher levels of nitric oxide when compared to static controls. Elimination of elevated ROS levels by free radical scavengers completely abolished the cardiomyogenic response of the cells. MicroRNA profile changes in stretched cells were detected for 39 miRNAs with 16 of the differentially expressed miRNAs related to heart development. The use of stem cells in combination with mechanical strain prior to their delivery in vivo may pose a valuable alternative for the treatment of myocardial infarction and merits further exploration for its capacity to augment the already observed beneficial effects of cellular therapies.
机译：近年来，用于治疗心肌梗死的细胞疗法已被证明是一种宝贵的工具，并为恢复正常心脏功能的可能性提供了令人鼓舞的证据。然而，对于此类应用的最佳电池来源、预处理方法和递送技术，仍然存在问题。本研究探讨了使用来自神经嵴并从成人牙周韧带分离的干细胞群以及短期机械应变作为心肌发生的诱导剂，并可能用于细胞心肌成形术的预处理刺激。在我们定制的生物反应器中，细胞受到短期动态机械张力的影响，并分析了心肌致病性。机械应变在刺激仅 2 小时后就引起了细胞的心肌反应。机械应变激活和易位心脏特异性转录因子 GATA4、MEF2C 和 Nkx2.5，并诱导肌动蛋白和心肌肌钙蛋白 T 蛋白的表达。与静态对照相比，机械应变导致的一氧化氮水平明显升高。通过自由基清除剂消除升高的ROS水平完全消除了细胞的心肌原反应。在拉伸细胞中检测到 39 个 miRNA 的 MicroRNA 谱变化，其中 16 个差异表达的 miRNA 与心脏发育相关。在体内递送之前，将干细胞与机械菌株结合使用可能是治疗心肌梗死的有价值的替代方案，并且值得进一步探索其增强已观察到的细胞疗法有益效果的能力。

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