Gamma radiation induces senescence in human adult mesenchymal stem cells from bone marrow and periodontal ligaments
Gamma radiation induces senescence in human adult mesenchymal stem cells from bone marrow and periodontal ligaments
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DOI：
10.3109/09553002.2012.666001
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发表时间：
2012-05-01
影响因子：
2.6
通讯作者：
Rezacova, Martina
中科院分区：
文献类型：
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作者：
Cmielova, Jana;Havelek, Radim;Rezacova, Martina
目的：骨髓间充质干细胞(BM-MSC)和牙周韧带间充质干细胞(PLSC)是一种具有高增殖能力和自我更新能力的细胞。这些细胞在基因毒性应激条件下的特征有助于评估它们的未来用途。本研究旨在探讨电离辐射对人骨髓间充质干细胞和骨髓间充质干细胞的影响。方法：用Co-60照射人骨髓间充质干细胞和骨髓间充质干细胞，观察13d后细胞的存活、增殖、凋亡和衰老情况，以及相关蛋白表达和磷酸化状态的变化。结果：剂量在20Gy以下的照射可显著抑制细胞增殖，但对细胞存活率无明显影响。肿瘤抑制蛋白53(P53)的活化及其在丝氨酸15和392上的磷酸化从照射后第1天开始检测到，并持续到第13天。细胞周期蛋白依赖性激酶抑制因子1A(p21(Cip1/Waf1))的表达增加。细胞周期停滞于G2期。我们检测到的不是细胞凋亡，而是应激诱导的早衰的特征：细胞周期蛋白依赖性激酶抑制因子2A(p16(INK4a))的增加和衰老相关的β-半乳糖苷酶活性的增加。结论：从骨髓和牙周膜分离的间充质干细胞通过诱导应激诱导的早衰来响应电离辐射，它们的辐射反应没有明显的差异。
Purpose: Mesenchymal stem cells isolated from bone marrow (BM-MSC) and periodontal ligament (PLSC) are cells with high proliferative potential and ability to self-renewal. Characterization of these cells under genotoxic stress conditions contributes to the assessment of their prospective usage. The aim of our study was to evaluate changes in BM-MSC and PLSC caused by ionizing radiation.Methods: Human BM-MSC and PLSC were irradiated with the doses up to 20 Gy by Co-60 and observed 13 days; viability, proliferation, apoptosis and senescence induction, and changes in expression and phosphorylation status of related proteins were studied.Results : Irradiation with the doses up to 20 Gy significantly reduces proliferation, but has no significant effect on cell viability. The activation of tumor suppressor protein 53 (p53) and its phosphorylations on serines 15 and 392 were detected from the first day after irradiation by 20 Gy and remained elevated to day 13. Expression of cyclin-dependent kinases inhibitor 1A (p21(Cip1/Waf1)) increased. The cell cycle was arrested in G2 phase. Instead of apoptosis we have detected hallmarks of stress-induced premature senescence: increase in cyclin-dependent kinases inhibitor 2A (p16(INK4a)) and increased activity of senescence-associated beta-galactosidase.Conclusion : Mesenchymal stem cells isolated from bone marrow and periodontal ligament respond to ionizing radiation by induction of stress-induced premature senescence without apparent differences in their radiation response.