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比较短期和长期培养中氧化应激对人成年和围产期组织来源干细胞衰老模式的影响。

Comparison of Oxidative Stress Effects on Senescence Patterning of Human Adult and Perinatal Tissue-Derived Stem Cells in Short and Long-term Cultures.

机构信息

Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.

National Laboratory of Molecular Biology and Stem Cell Bioengineering of the National Institute of Biostructures and Biosystems (NIBB) - Eldor Lab, at the Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy.

出版信息

Int J Med Sci. 2018 Oct 20;15(13):1486-1501. doi: 10.7150/ijms.27181. eCollection 2018.

DOI:10.7150/ijms.27181
PMID:30443170
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6216057/
Abstract

Human Mesenchymal Stem Cells (hMSCs) undergo senescence in lifespan. In most clinical trials, hMSCs experience long-term expansion to increase cell number prior to transplantation, which unfortunately leads to cell senescence, hampering post-transplant outcomes. Hydrogen peroxide (HO) represents a rapid, time and cost-effective tool, commonly used as oxidative stress tantalizing the stem cell ability to cope with a hostile environment, recapitulating the onset and progression of cellular senescence. Here, HO at different concentrations (ranging from 50 to 400 μM) and time exposures (1 or 2 hours - h), was used for the first time to compare the behavior of human Adipose tissue-derived Stem Cells (hASCs) and human Wharton's Jelly-derived MSCs (hWJ-MSCs), as representative of adult and perinatal tissue-derived stem cells, respectively. We showed timely different responses of hASCs and hWJ-MSCs at low and high subculture passages, concerning the cell proliferation, the cell senescence-associated β-Galactosidase activity, the capability of these cells to undergo passages, the morphological changes and the gene expression of (, alias ) and (, alias ) post HO treatments. The comparison between the hASC and hWJ-MSC response to oxidative stress induced by HO is a useful tool to assess the biological mechanisms at the basis of hMSC senescence, but it could also provide two models amenable to test putative anti-senescence modulators and develop anti-senescence strategies.

摘要

人骨髓间充质干细胞(hMSCs)在寿命过程中会衰老。在大多数临床试验中,hMSCs 在移植前经历长期扩增以增加细胞数量,这不幸导致细胞衰老,从而阻碍移植后的结果。过氧化氢(HO)是一种快速、省时且经济有效的工具,通常用作氧化应激,以激发干细胞应对恶劣环境的能力,重现细胞衰老的发生和进展。在这里,首次使用不同浓度(范围从 50 到 400 μM)和时间暴露(1 或 2 小时 - h)的 HO 来比较人脂肪组织来源的干细胞(hASCs)和人 Wharton 胶来源的间充质干细胞(hWJ-MSCs)的行为,分别作为成人和围产期组织来源的干细胞的代表。我们显示了 hASCs 和 hWJ-MSCs 在低和高亚培养传代时的不同反应,涉及细胞增殖、衰老相关的β-半乳糖苷酶活性、这些细胞的传代能力、形态变化和基因表达(,别名)和(,别名)在 HO 处理后。hASC 和 hWJ-MSC 对 HO 诱导的氧化应激的反应比较是评估 hMSC 衰老基础上的生物学机制的有用工具,但它也可以提供两种模型,适用于测试潜在的抗衰老调节剂并开发抗衰老策略。

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