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Functional responses of human adipose tissue-derived mesenchymal stem cells to metal oxide nanoparticles in vitro

机译:人脂肪组织间充质干细胞在体外对金属氧化物纳米粒子的功能反应

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摘要

Nanoparticles (NPs) are frequently applied in biomedical applications. The use of human mesenchymal stem cells (hMSC) in biomedicine is pivotal, especially in oncology and tissue engineering. Titanium dioxide (TiO_2) and zinc oxide (ZnO) NPs are interesting agents in experimental oncology and stem cells are discussed to be a potential vehicle for NPs to tumor sites. However, little is known about hazardous effects of NPs in hMSC. The aim of the present study was to analyze functional impairment of hMSC by ZnO- and TiO_2-NPs. Cytotoxic effects of NPs were evaluated by the MTT-assay. Furthermore, multi-differentiation capacity, spheroid formation and migration were assessed. The immunophenotype was observed by flow cytometry. Cytotoxic effects were observed at 625 nM ZnO-NPs whereas no cytotoxicity was seen in hMSC by TiO_2-NPs. The differentiation capacity of hMSC into osteogenic and adipose lineages was unchanged. A long-term period cultivation of hMSC for 3 weeks after NP exposure revealed a persistence of NPs in the cytoplasm. The migration capability was impaired whereas the ability to form spheroids was not affected. Flow cytometric analysis revealed distinct alteration of cell surface markers CD 90 and CD 73. Major functional properties of hMSC were unaffected by TiO_2- and ZnO-NPs. However, restricted migration might critically influence wound healing capacity. Further information is needed to assess the clinical impact of these findings.
机译:纳米颗粒(NPs)经常用于生物医学领域。人间充质干细胞(hMSC)在生物医学中的应用至关重要,特别是在肿瘤学和组织工程学中。二氧化钛(TiO_2)和氧化锌(ZnO)NP是实验肿瘤学中令人关注的试剂,干细胞被认为是NPs进入肿瘤部位的潜在载体。但是,关于NP在hMSC中的有害作用知之甚少。本研究的目的是分析ZnO-和TiO_2-NP对hMSC的功能损害。 NPs的细胞毒性作用通过MTT测定法评估。此外,评估了多分化能力,球体的形成和迁移。通过流式细胞术观察免疫表型。在625 nM ZnO-NPs处观察到细胞毒性作用,而TiO_2-NPs在hMSC中未观察到细胞毒性。 hMSC分化为成骨和脂肪谱系的能力没有改变。 NP暴露后3周的hMSC的长期培养显示出NP在细胞质中的持久性。迁移能力受损,而形成球体的能力未受影响。流式细胞仪分析揭示了细胞表面标记CD 90和CD 73的明显变化。hMSC的主要功能特性不受TiO_2-和ZnO-NP的影响。但是,有限的迁移可能会严重影响伤口的愈合能力。需要更多信息来评估这些发现的临床影响。

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