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IGF-1 rescues human intervertebral annulus cells from in vitro stress-induced premature senescence.
Growth Factors ( IF 1.8 ) Pub Date : 2008-11-21 , DOI: 10.1080/08977190802273814
Helen E Gruber 1 , Gretchen L Hoelscher , Jane A Ingram , Synthia Bethea , Edward N Hanley
Affiliation  

The aging human intervertebral disc contains a sizeable population of senescent cells. Since senescent cells cannot divide, senescence reduces the disc's ability to generate new cells to replace existing ones lost to necrosis or apoptosis. The objectives of the present work were: (1) to develop a reliable in vitro model for stress-induced premature senescence in human annulus cells, and (2) to investigate the potential for insulin-like growth factor-1 (IGF-1) to prevent or ameliorate senescence in vitro. The developed experimental model employs a 2 h exposure to 50 microM hydrogen peroxide; immunocytochemical localization of senescence associated-beta-galactosidase at pH 6.0 was used as the marker for senescent cells, and the percentage of senescent cells quantified after 3 days of culture. Nine sets of annulus cells were obtained from eight human surgical disc specimens; cells were tested with 0, 50, 100 or 500 ng/ml IGF-1. Although 50 or 100 ng/ml IGF-1 did not significantly alter the percentage of senescent cells, a significant reduction was present following exposure to 500 ng/ml IGF-1 (control, 56.3% +/- 8.5 (9); mean +/- SEM, (n) vs. treated, 39.6% +/- 6.6 (9), p = 0.0009). These novel findings point to the value of continued research towards development of future biologic therapies designed to reduce cell senescence in degenerating human discs.

中文翻译:

IGF-1可从人体内应力诱导的过早衰老中拯救人的椎间盘环细胞。

老化的人椎间盘包含大量衰老细胞。由于衰老的细胞无法分裂,衰老会降低椎间盘生成新细胞的能力,以取代因坏死或凋亡而丢失的现有细胞。本工作的目标是:(1)建立可靠的体外模型用于应激诱导人环细胞过早衰老,和(2)研究胰岛素样生长因子-1(IGF-1)的潜力预防或改善体外衰老。开发的实验模型采用暴露于50 microM过氧化氢中2小时的方法;在pH 6.0下将衰老相关的β-半乳糖苷酶的免疫细胞化学定位用作衰老细胞的标志物,并在培养3天后对衰老细胞的百分比进行定量。从八个人类手术盘标本中获得了九套环细胞;用0、50、100或500 ng / ml IGF-1测试细胞。尽管50或100 ng / ml IGF-1不会显着改变衰老细胞的百分比,但暴露于500 ng / ml IGF-1后仍显着降低(对照,56.3%+/- 8.5(9);平均值+ SEM,(n)对处理后,39.6%+ /-6.6(9),p = 0.0009)。这些新颖的发现表明,继续进行研究对于开发旨在减少变性人椎间盘中细胞衰老的未来生物疗法的价值。平均+/- SEM,(n)vs.治疗,39.6%+/- 6.6(9),p = 0.0009)。这些新颖的发现表明,继续进行研究对于开发旨在减少变性人椎间盘中细胞衰老的未来生物疗法的价值。平均+/- SEM,(n)vs.治疗,39.6%+/- 6.6(9),p = 0.0009)。这些新颖的发现表明,继续进行研究对于开发旨在减少变性人椎间盘中细胞衰老的未来生物疗法的价值。
更新日期:2019-11-01
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