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Acta Biomater. 2011 Jan;7(1):347-54. doi: 10.1016/j.actbio.2010.08.003. Epub 2010 Aug 13.

Uptake and intracellular distribution of silver nanoparticles in human mesenchymal stem cells.

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Bergmannsheil University Hospital/Surgical Research, Ruhr University Bochum, Germany.


Silver nanoparticles (Ag-NP) are widely used due to their well-known antibacterial effects. In medicine Ag-NP have found applications as wound dressings, surgical instruments and bone substitute biomaterials, e.g. silver-containing calcium phosphate cements. Depending on the coating technique, during resorption of a biomaterial Ag-NP may come into close contact with body tissues, including human mesenchymal stem cells (hMSC). Despite the widespread uses of Ag-NP, there is a serious lack of information concerning their biological effects on human cells. In this study the uptake of Ag-NP into hMSC has been analyzed and the intracellular distribution of Ag-NP after exposure determined. Non-agglomerated (dispersed) Ag-NP from the cell culture medium were detected as agglomerates of nanoparticles within the hMSC by combined focused ion beam/scanning electron microscopy. The silver agglomerates were typically located in the perinuclear region, as determined by light microscopy. Specific staining of cellular structures (endo-lysosomes, nuclei, Golgi complex and endoplasmatic reticulum) using fluorescent probes showed that the silver nanoparticles occurred mainly within endo-lysosomal structures, not in the cell nucleus, endoplasmic reticulum or Golgi complex. Quantitative determination of the uptake of Ag-NP by flow cytometry (scattergram analysis) revealed a concentration-dependent uptake of the particles which was significantly inhibited by chlorpromazine and wortmannin but not by nystatin, indicating clathrin-dependent endocytosis and macropinocytosis as the primary uptake mechanisms.

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