The effects of mechanical stress on the growth, differentiation, and paracrine factor production of cardiac stem cells.
The effects of mechanical stress on the growth, differentiation, and paracrine factor production of cardiac stem cells.
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DOI：
10.1371/journal.pone.0028890
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Li TS
中科院分区：
文献类型：
--
作者：
Kurazumi H;Kubo M;Ohshima M;Yamamoto Y;Takemoto Y;Suzuki R;Ikenaga S;Mikamo A;Udo K;Hamano K;Li TS
干细胞疗法已在临床上用于修复受损的心脏，心脏干细胞被认为是最有效的干细胞候选者之一。跳动的心脏的特征在于动态机械应力，这可能对干细胞治疗产生重大影响。本研究的目的是探讨机械应力如何影响心脏干细胞的生长、分化及其旁分泌因子的释放。在这项研究中，将人心脏干细胞接种在硅室中，然后通过周期性拉伸刺激（60个周期/分钟，120%伸长）诱导机械应力。使用在非拉伸硅室中生长的细胞作为对照。我们的结果显示，与对照组相比，机械拉伸显著减少了拉伸组24小时后存活细胞的总数，减少了Ki-67阳性细胞，增加了TUNEL阳性细胞。有趣的是，在12小时内，机械拉伸显著增加了炎性细胞因子IL-6和IL-1β以及血管生成生长因子VEGF和bFGF从细胞中的释放。此外，机械拉伸显著降低了c-kit阳性干细胞的百分比，但增加了心肌肌钙蛋白-I和平滑肌肌动蛋白在细胞中的表达拉伸后3天。使用传统的拉伸模型，我们证明了机械应力抑制心脏干细胞的生长和增殖，增强其释放炎性细胞因子和血管生成因子，并改善其肌源性分化。这种体外方法的发展可能有助于阐明干细胞治疗心力衰竭的复杂机制。
Stem cell therapies have been clinically employed to repair the injured heart, and cardiac stem cells are thought to be one of the most potent stem cell candidates. The beating heart is characterized by dynamic mechanical stresses, which may have a significant impact on stem cell therapy. The purpose of this study is to investigate how mechanical stress affects the growth and differentiation of cardiac stem cells and their release of paracrine factors. In this study, human cardiac stem cells were seeded in a silicon chamber and mechanical stress was then induced by cyclic stretch stimulation (60 cycles/min with 120% elongation). Cells grown in non-stretched silicon chambers were used as controls. Our result revealed that mechanical stretching significantly reduced the total number of surviving cells, decreased Ki-67-positive cells, and increased TUNEL-positive cells in the stretched group 24 hrs after stretching, as compared to the control group. Interestingly, mechanical stretching significantly increased the release of the inflammatory cytokines IL-6 and IL-1β as well as the angiogenic growth factors VEGF and bFGF from the cells in 12 hrs. Furthermore, mechanical stretching significantly reduced the percentage of c-kit-positive stem cells, but increased the expressions of cardiac troponin-I and smooth muscle actin in cells 3 days after stretching. Using a traditional stretching model, we demonstrated that mechanical stress suppressed the growth and proliferation of cardiac stem cells, enhanced their release of inflammatory cytokines and angiogenic factors, and improved their myogenic differentiation. The development of this in vitro approach may help elucidate the complex mechanisms of stem cell therapy for heart failure.
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影响因子：
2.4
作者：
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通讯作者：
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5.2
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影响因子：
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作者：
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