Evaluation of age effects on doxorubicin-induced toxicity in mesenchymal stem cells.
Evaluation of age effects on doxorubicin-induced toxicity in mesenchymal stem cells.
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DOI：
10.14196/mjiri.31.98
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发表时间：
2017
影响因子：
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通讯作者：
Ali-Esfahani T
中科院分区：
文献类型：
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作者：
Bashiri Dezfouli A;Pourfathollah AA;Salar-Amoli J;Khosravi M;Nikogoftar-Zarif M;Yazdi M;Ali-Esfahani T
背景：阿霉素在骨髓中聚集，引起基因毒性作用，从而降低细胞的修复能力。本研究旨在体外评价年龄对阿霉素诱导间充质干细胞（MSCs）细胞毒性的影响。方法：分别对1、8、16月龄BALB/c雌性小鼠的MSCs进行分离、表征，并在细胞生长培养基中进行评价。采用流式细胞术和乳酸脱氢酶（LDH）释放法测定3组小鼠MSCs在阿霉素（25、50、100、200、400、800、1200 nM）作用24 h后的细胞毒性。结果：青年小鼠1只，中年小鼠8只，老年小鼠16只，分离后的MSCs经流式细胞术测定IC50值分别为和。有趣的是，这两种方法测定细胞毒性的结果是一致的，大约25 nM的浓度被认为是不同年龄的共同亚致死剂量。结论：中年小鼠骨髓间充质干细胞对该药的毒性作用具有较强的抗性。此外，从老年小鼠中分离的间充质干细胞对化疗及其副作用（如细胞增殖和活力的破坏）最为敏感。这些破坏可归因于随着年龄的增长功能和生理过程的改变。根据年龄和个体的敏感性，确定适当的阿霉素药物浓度来破坏癌细胞，可以最大限度地减少毒性
Background: Doxorubicin, by aggregating in bone marrow, causes genotoxic effects, and thus reduces the repair ability of cells. The present study was conducted as an in vitro evaluation of age effects on the cytotoxicity induced by doxorubicin in mesenchymal stem cells (MSCs). Methods: The MSCs of female BALB/c mice aged 1, 8, and 16 months were separated, characterized, and subsequently evaluated in cellular growth media. After 24 hours, exposure of the MSCs of the 3 groups of mice to doxorubicin (25, 50, 100, 200, 400, 800, 1200 nM) and cytotoxicity were assessed, and the sublethal dose was determined using flow cytometry technique and lactate dehydrogenase (LDH) release assay. Results: The IC50 values determined by flow cytometry for the separated MSCs of 1 young, 8 middle- aged, and 16 old mice were and respectively. Interestingly, the results of these 2 methods in determining cytotoxicity were in agreement, and a concentration of approximately 25 nM was considered to be the shared sublethal dose for different ages. Conclusion: The results indicated that MSCs of middle-aged mice were more resistant to the toxic effects of the drug. Besides, MSCs separated from the old mice were the most sensitive to chemotherapy and its side effects such as disruptions of cell proliferation and viability. These disruptions can be ascribed to the alteration of function and physiological processes with age. Determining proper concentration of doxorubicin drug to destruct cancerous cells based on age and individual sensitivity can minimize the amount of toxicity