Cellular Antioxidant Levels Influence Muscle Stem Cell Therapy
Cellular Antioxidant Levels Influence Muscle Stem Cell Therapy
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DOI：
10.1038/mt.2010.160
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发表时间：
2010-10-01
影响因子：
12.4
通讯作者：
Huard, Johnny
中科院分区：
文献类型：
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作者：
Drowley, Lauren;Okada, Masaho;Huard, Johnny
虽然细胞移植已被证明可以促进损伤后心脏功能的改善，但移植后细胞存活率低仍然限制了这种疗法的疗效。我们以前观察到，移植肌源性干细胞（MDSC）在急性心肌梗死小鼠模型中改善心脏功能的程度大于成肌细胞。MDSC的这种改善的再生能力与其增加的抗氧化剂水平有关，如谷胱甘肽（GSH）和超氧化物歧化酶。在目前的研究中，我们通过降低马来酸二乙酯的抗氧化剂水平或增加N-乙酰半胱氨酸（NAC）的抗氧化剂水平，证明了抗氧化剂水平对MDSC存活和心脏功能恢复的关键作用。抗氧化剂和促氧化剂处理均显著影响体外MDSC的存活。当NAC处理的MDSC移植到梗死心肌中时，我们观察到与注射未处理和马来酸二乙酯处理的细胞相比，心脏功能显著改善，瘢痕组织形成减少，CD 31（+）内皮细胞结构数量增加。这些结果表明，用NAC提高MDSC中抗氧化剂的水平可以显著影响其组织再生能力。
Although cellular transplantation has been shown to promote improvements in cardiac function following injury, poor cell survival following transplantation continues to limit the efficacy of this therapy. We have previously observed that transplantation of muscle-derived stem cells (MDSCs) improves cardiac function in an acute murine model of myocardial infarction to a greater extent than myoblasts. This improved regenerative capacity of MDSCs is linked to their increased level of antioxidants such as glutathione (GSH) and superoxide dismutase. In the current study, we demonstrated the pivotal role of antioxidant levels on MDSCs survival and cardiac functional recovery by either reducing the antioxidant levels with diethyl maleate or increasing antioxidant levels with N-acetylcysteine (NAC). Both the anti- and pro-oxidant treatments dramatically influenced the survival of the MDSCs in vitro. When NAC-treated MDSCs were transplanted into infarcted myocardium, we observed significantly improved cardiac function, decreased scar tissue formation, and increased numbers of CD31(+) endothelial cell structures, compared to the injection of untreated and diethyl maleate-treated cells. These results indicate that elevating the levels of antioxidants in MDSCs with NAC can significantly influence their tissue regeneration capacity.