Oxidative stress induces senescence in human mesenchymal stem cells
Oxidative stress induces senescence in human mesenchymal stem cells
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DOI：
10.1016/j.yexcr.2011.02.015
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发表时间：
2011-07-01
影响因子：
3.7
通讯作者：
Angele, Peter
中科院分区：
文献类型：
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作者：
Brandl, Anita;Meyer, Matthias;Angele, Peter
骨髓间充质干细胞（Mesenchymal stem cells，MSCs）在体内具有组织修复作用，是组织工程的重要细胞来源。它们的再生潜力因细胞衰老而受损。氧化应激对MSCs的影响尚不清楚。我们的研究旨在探讨骨髓间充质干细胞在急性或长期过氧化氢氧化剂刺激下的增殖潜力、细胞学特征和端粒相关的应激反应系统。端粒长度采用端粒限制性片段分析法测定，基因表达采用rtPCR法测定。亚致死剂量的氧化应激降低增殖率，诱导衰老的形态特征和衰老相关的β-半乳糖苷酶阳性。用过氧化氢长时间低剂量处理对细胞增殖或形态没有影响。亚致死和长期低剂量的氧化应激大大加速端粒磨损。急性氧化损伤后，p21在恢复到初始水平之前上调。TRF 1表达明显降低，TRF 2表达略有上调。SIRT 1和XRCC 5在氧化损伤后上调，并且在衰老细胞中表达水平增加。与成纤维细胞和软骨细胞相比，MSC表现出对氧化应激的耐受性增加，包括增殖、端粒生物学和基因表达，而衰老细胞的应激耐受性受损。(C)2011 Elsevier Inc. All rights reserved.
Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of MSCs, subject to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by rtPCR. Sub-lethal doses of oxidative stress reduced proliferation rates and induced senescent-morphological features and senescence-associated beta-galactosidase positivity. Prolonged low dose treatment with hydrogen peroxide had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. Following acute oxidant insult p21 was up-regulated prior to returning to initial levels. TRF1 was significantly reduced, TRF2 showed a slight up-regulation. SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells. Compared to fibroblasts and chondrocytes, MSCs showed an increased tolerance to oxidative stress regarding proliferation, telomere biology and gene expression with an impaired stress tolerance in aged cells. (C) 2011 Elsevier Inc. All rights reserved.