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首页> 外文期刊>Journal of applied toxicology >In vitro toxicity screening of magnetite nanoparticles by applying mesenchymal stem cells derived from human umbilical cord lining
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In vitro toxicity screening of magnetite nanoparticles by applying mesenchymal stem cells derived from human umbilical cord lining

机译：通过施用来自人脐带衬里的间充质干细胞来体外毒性筛选磁铁矿纳米粒子

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Abstract Despite the growing interest in nanoparticles (NPs), their toxicity has not yet been defined and the development of new strategies and predictive models are required. Human stem cells (SCs) offer a promising and innovative cell‐based model. Among SCs, mesenchymal SCs (MSCs) derived from cord lining membrane (CL) may represent a new species‐specific tool for establishing efficient platforms for primary screening and toxicity/safety testing of NPs. Superparamagnetic iron oxide NPs, including magnetite (Fe 3 O 4 NPs), have aroused great public health and scientific concerns despite their extensive uses. In this study, CL‐MSCs were characterized and applied for in vitro toxicity screening of Fe 3 O 4 NPs. Cytotoxicity, internalization/uptake, differentiation and proliferative capacity were evaluated after exposure to different Fe 3 O 4 NP concentrations. Data were compared with those obtained from bone marrow (BM)‐MSCs. We observed, at early passages (P3), that: (1) cytotoxicity occurred at 10?μg/mL in CL‐MSCs and 100?μg/mL in BM‐MSCs (no differences in toxicity, between CL‐ and BM‐MSCs, were observed at higher dosage, 100‐300?μg/mL); (2) cell density decrease and monolayer features loss were affected at ≥50?μg/mL in CL‐MSCs only; and (3) NP uptake was concentration‐dependent in both MSCs. After 100?μg/mL Fe 3 O 4 NP exposures, the capacity of proliferation was decreased (P5‐P9) in CL‐MSCs without morphology alteration. Moreover, a progressive decrease of intracellular Fe 3 O 4 NPs was observed over culture time. Antigen surface expression and multilineage differentiation were not influenced. These findings suggest that CL‐MSCs could be used as a reliable cell‐based model for Fe 3 O 4 NP toxicity screening evaluation and support the use of this approach for improving the confidence degree on the safety of NPs to predict health outcomes.
机译：摘要尽管对纳米颗粒（NPS）的兴趣日益生长，但尚未确定它们的毒性，并且需要开发新的策略和预测模型。人干细胞（SCS）提供了有希望和创新的细胞基础模型。在SCS中，源自脐带膜（CL）的间充质SCS（MSCs）可以代表一种用于建立高效平台的新物种特异性工具，用于对NPS的初级筛选和毒性/安全测试建立有效的平台。尽管他们广泛的用途，超顺磁性氧化铁NPS（包括磁铁矿）在该研究中，CL-MSCs的特征和应用于Fe 3 O 4 NPS的体外毒性筛选。在暴露于不同Fe 3 O 4 NP浓度后评估细胞毒性，内化/摄取，分化和增殖能力。将数据与来自骨髓（BM）-MSC获得的数据进行比较。在早期通道（P3）处观察到：（1）CL-MSC中的10〜μg/ ml的细胞毒性和BM-MSC中的100·μg/ mL（在CL-和BM-MSC之间没有差异差异，在较高剂量，100-300×μg/ ml处观察到; （2）细胞密度降低，单层特征损失仅在CL-MSCS中受到≥50Ωμg/ mL; （3）NP吸收浓度依赖于两个MSC。在100℃/ ml FE 3 O 4 NP暴露后，CL-MSCs中的增殖能力降低（P5-P9），而不会改变形态。此外，在培养时间上观察到细胞内Fe 3 O 4 NP的逐渐降低。抗原表面表达和多重分化不影响。这些发现表明，CL-MSCs可用作Fe 3 O 4 NP毒性筛选评估的可靠细胞的模型，并支持使用这种方法来提高NPS安全性以预测健康结果的置信度。

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