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JCR 2016
جستجوی مقالات
چهارشنبه 26 آذر 1404
Cell Journal
، جلد ۱۷، شماره Suppl ۱، صفحات ۱۵-۱۵
عنوان فارسی
چکیده فارسی مقاله
کلیدواژههای فارسی مقاله
عنوان انگلیسی
Is-16: Mouse Bone Marrow Mesenchymal Stem Cells, as A Model for Evaluating Nanomaterial Toxicity
چکیده انگلیسی مقاله
Mesenchymal stem cells are multi potent progenitor stem cells that have the ability to differentiate into atleast three lineages such as chondrocytes, osteoblasts and adipocytes and are one of the most widely used cells in tissue engineering. Owing to high proliferative and differentiation capacity, Mesenchymal Stem cell culture could be considered as a model of target tissue in the body and thereby mimics the tissue response to the exposure of nanomaterials. For these reasons, stem cells could be exploited for developing in vitro model systems to evaluate the toxicity of nanomaterials. The objective of the study is to investigate the mouse bone marrow mesenchymal stem cells (BMSCs) as a model for evaluating the nanomaterial toxicity. Stem cells isolated from the bone marrow of Swiss albino mice (BMSCs) were used for the study. The BMSC were cultured and maintained in DMEM-HG medium and are further characterized for the expression of MSCs surface markers CD44, CD90 and negative marker CD45. Confluent cells obtained after third passage were used for the toxicity evaluation. Different concentrations of HANPs (hydroxyapatite nanoparticles) and ZONPs (zinc oxide nanoparticles) were exposed to BMSCs. Various toxic parameters such as cytotoxicity, reactive oxygen species (ROS) production and apoptosis by Annexin V/PI assay using FACS were evaluated. The results of the MTT assay indicated that HANPs does not induce cytotoxicity up to 800 μg/mL. It was also observed that oxidative stress related apoptosis and ROS production following HANPs treatment was similar to that of control. Further, ZnO NPs significantly affects cellular viability in a dose dependent manner. Formation of ROS was found to be the mechanism of cellular toxicity. The release of Zn+ ions from the nanoparticles, due to the instability of ZnO NPs in the acidic compartment of lysosomes also increases the ROS generation. In addition to increased ROS production, damage of lysosomal membrane and the activation of executioner caspase-3 and caspase-7 were observed which eventually ends in apoptosis. The present study concludes that the in house synthesized HANPs are non-toxic/safe at the molecular level suggesting that the HANPs are compatible to BMSCs. However, a dose dependent toxicological response of ZnONPs to bone marrow mesenchymal stem cells are observed as evidenced from the potential to induce cytotoxicity and ROS generation which in turn affects the cytoskeleton organization and disrupts the intracellular interaction. Activation of caspases and flow cytometry data reveals oxidative stress mediated apoptosis. Furthermore the toxicity mechanism of ZnONP interaction with BMSC elucidated in the present study followed both the mitochondria and lysosome mediated programmed cell death. Based on the parameters evaluated, it is concluded that BMSCs could be used as an alternative model for evaluating the preliminary toxicity of nanomaterials.
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نویسندگان مقاله
pv mohanan | pv mohanan
نشانی اینترنتی
http://celljournal.org/journal/article/abstract/40
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