Skip to main content

Advertisement

SpringerLink
Log in

Studies on the biocompatibility and the interaction of silver nanoparticles with human mesenchymal stem cells (hMSCs)

  • Original Article
  • Published:
Langenbeck's Archives of Surgery Aims and scope Submit manuscript

Abstract

Purpose

Silver nanoparticles (Ag-NPs) are widely used in different areas, e.g., in the food, electronic, or clothing industry due to well-known slow-release antiseptic activities. Despite the widespread use of nanosilver, there is a serious lack of information concerning the biological activities of nanosilver on human tissue cells.

Materials and methods

In this study, the influence of spherical Ag-NPs (diameter about 100 nm) on the biological functions (proliferation, cytokine release, and chemotaxis) of human mesenchymal stem cells (hMSCs) was analyzed.

Results

The results showed a concentration-dependent activation of hMSCs at nanosilver levels of 2.5 μg mL−1, and cytotoxic cell reactions occurred at Ag-NPs concentrations above 5 μg mL−1. Cell proliferation and the chemotaxis of hMSC both decreased with increasing Ag-NPs concentrations. Different effects on the cytokine release from hMSCs were observed in the presence of Ag-NPs and Ag+ ions. The release of IL-8 was significantly increased at high but noncytotoxic concentrations of Ag-NPs (2.5 μg mL−1). In contrast, the levels of IL-6 and VEGF were concomitantly decreased compared to the control group. The synthesis of IL-11 was not affected at different Ag-NP concentrations. The agglomeration tendency of Ag-NPs in different biological media increased with a high electrolyte content, e.g., in RPMI. However, complexation with fetal calf serum in the cell culture media stabilized the Ag-NPs against agglomeration.

Conclusion

In summary, the results showed that Ag-NPs exert cytotoxic effects on hMSCs at high concentrations but also induce cell activation (as analyzed by the release of IL-8) at high but nontoxic concentrations of nanosilver.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Lok C, Ho C, Chen R, He Q, Yu W, Sun H, Tam P, Chiu J, Che C (2007) Silver nanoparticles:partial oxidation and antibacterial activities. J Biol Inorg Chem 12:527–534

    Article  PubMed  CAS  Google Scholar 

  2. Ahmed M, Karns M, Goodson M, Rowe J, Hussain S, Schlager J, Hong Y (2008) DNA damage response to different surface chemistry of silver nanoparticles in mammalian cells. Toxicol Appl Pharmacol 233:404–410

    Article  Google Scholar 

  3. Cho K, Park J, Osaka T, Park S (2005) The study of antimicrobial activity and preservative effects of nanosilver ingredient. Electrochim Acta 51:956–960

    Article  CAS  Google Scholar 

  4. Jung W, Koo H, Kim K, Shin S, Kim S, Park Y (2008) Antibacterial activity and mechanism of action of the silver ion in Staphylococcus aureus and Escherichia coli. Appl Environ Microbiol 74:2171–2178

    Article  PubMed  CAS  Google Scholar 

  5. Kim J, Kuk E, Yu K, Kim J, Park S, Lee H, Kim S, Park Y, Park YH, Hwang C, Kim Y, Lee Y, Jeong D, Cho M (2007) Antimicrobial effects of silver nanoparticles. Nanomedicine 3:95–101

    PubMed  CAS  Google Scholar 

  6. Chen X, Schluesener HJ (2008) Nanosilver: A nanoproduct in medical application. Toxicol Lett 176:1–12

    Article  PubMed  CAS  Google Scholar 

  7. Matsumura Y, Yoshikata K, Kunisaki S, Tsuchido T (2003) Mode of bactericidal action of silver zeolite and its comparison with that of silver nitrate. Appl Environ Microbiol 69:4278–4281

    Article  PubMed  CAS  Google Scholar 

  8. Roe D, Karandikar B, Bonn-Savage N, Gibbins B, Roullet JB (2008) Antimicrobial surface functionalization of plastic catheters by silver nanoparticles. J Antimicrob Chemother 61:869–876

    Article  PubMed  CAS  Google Scholar 

  9. Gupta A, Matsui K, Lo JF, Silver S (1999) Molecular basis for resistance to silver cations in Salmonella. Nat Med 5:183–188

    Article  PubMed  CAS  Google Scholar 

  10. Morones J, Elechiguerra J, Camacho A, Holt K, Kouri J, Ramirez J, Yacaman M (2005) The bactericidal effect of silver naoparticles.. Nanotechnology 16:2346–2353

    Article  CAS  Google Scholar 

  11. Feng Q, Wu J, Chen G, Cui F, Kim T, Kim J (2000) A mechanistic study of the antibacterial effect of silver ions on Escherichia coli and Staphylococcus aureus. J Biomed Mater Res 52:662–668

    Article  PubMed  CAS  Google Scholar 

  12. Alt V, Bechert T, Steinrücke P, Wagener M, Seidel P, Dingeldein E, Domann E, Schnettler R (2004) An in vitro assessment of the antibacterial properties and cytotoxicity of nanoparticulate silver bone cement. Biomaterials 25:4383–4391

    Article  PubMed  CAS  Google Scholar 

  13. Kim K, Sung W, Moon S, Choi J, Kim J, Lee D (2008) Antifungal effect of silver nanoparticles on dermatophytes. J Microbiol Biotechnol 18:1482–1484

    PubMed  Google Scholar 

  14. Elechiguerra J, Burt J, Morones J, Camacho-Bragado A, Gao X, Lara HH, Yacaman J (2005) Interaction of silver nanoparticles with HIV-1. J Nanobiotechnology 3:6–15

    Article  PubMed  Google Scholar 

  15. Modak S, Sampath L, Fox C (1988) Combined topical use of silver sulfadiazine and antibiotics as a possible solution to bacterial resistance in burn wounds. J Burn Care Rehabil 9:359–363

    Article  PubMed  CAS  Google Scholar 

  16. Silver S (2003) Bacterial silver resistance: molecular biology and uses and misuses of silver compounds. FEMS Microbiol Rev 27:341–353

    Article  PubMed  CAS  Google Scholar 

  17. Li X, Nikaido H, Williams K (1997) Silver-resistant mutants of Escherichia coli display active efflux of Ag+ and are deficient in porins. J Bacteriol 179:6127–6132

    PubMed  CAS  Google Scholar 

  18. Pittenger M, Mackay A, Beck S, Jaiswal R, Douglas R, Mosca J, Moorman M, Simonetti D, Craig S, Marshak D (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  PubMed  CAS  Google Scholar 

  19. Baksh D, Song L, Tuan RS (2004) Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med 8:301–316

    Article  PubMed  CAS  Google Scholar 

  20. Im S, Lee Y, Wiley B, Xia Y (2005) Large-scale synthesis of silver nanocubes: the role of HCl in promoting cube perfection and monodispersity. Angew Chem 44:2154–2157

    Article  CAS  Google Scholar 

  21. Schildhauer T, Chapman J, Muhr G, Köller M (2006) Cytokine release of mononuclear leukocytes (PBMC) after contact to a carbonated calcium phosphate bone cement. J Biomed Mater Res 78:104–109

    Article  CAS  Google Scholar 

  22. Murdock R, Braydich-Stolle L, Schrand A, Schlager J, Hussain S (2008) Characterization of nanomaterial dispersion in solution prior to in vitro exposure using dynamic light scattering technique. Toxicol Sci 101:239–253

    Article  PubMed  CAS  Google Scholar 

  23. Mishima Y, Lotz M (2008) Chemotaxis of human articular chondrocytes and mesenchymal stem cells. J Orthop Res 26:1407–1412

    Article  PubMed  Google Scholar 

  24. Kim D, Yoo K, Choi K, Choi J, Choi S, Yang S, Yang Y, Im H, Kim K, Jung H, Sung K, Koo H (2005) Gene expression profile of cytokine and growth factor during differentiation of bone-marrow-derived mesenchymal stem cells. Cytokine 31:119–126

    Article  PubMed  CAS  Google Scholar 

  25. Griffitt R, Luo J, Gao J, Bonzongo J, Barber D (2008) Effects of particle composition ans species on toxicity of metallic nanomaterials in aquatic organisms. Environ Toxicol Chem 27:1972–1978

    Article  PubMed  CAS  Google Scholar 

  26. Cohen M, Stern J, Vanni A, Kelley R, Baumgart E, Field D, Libertino J, Summerhayes I (2007) In vitro analysis of a nanocrystalline silver-coated surgical mesh. Surg Infect (Larchmt) 8:397–403

    Article  Google Scholar 

  27. Tautenhahn J, Meyer F, Buerger T, Schmidt U, Lippert H, Koenig W, Koenig B (2008) Interaction of neutrophils with silver-coated vascular polyester grafts, Langenbecks Arch. Surg., in print

  28. Roe D, Karandikar B, Bonn-Savage N, Gibbins B, Roullet J (2008) Antimicrobial surface functionalization ofplastic catheters by silver nanoparticles. J Antimicrob Chemother 61:869–876

    Article  PubMed  CAS  Google Scholar 

  29. Trop M, Novak M, Rodl S, Hellborn B, Kroell W, Goessler W (2003) Silver-coated dressing acticoat caused raised liver enzymes and argyria-like symptoms in burn patient. J Trauma 60:648–652

    Article  Google Scholar 

  30. Navarro E, Piccapitra F, Wagner B, Marconi F, Kaegi R, Odzak N, Sigg L, Behra R (2008) Toxicity of silver nanoparticles to Chlamydomonas reinhardtii. Environ Sci Technol 42:8959–8964

    Article  PubMed  CAS  Google Scholar 

  31. Hsin Y, Chen C, Huang S, Shih T, Lai P, Chueh P (2008) The apoptotic effect of nanosilver is mediated by a ROS- and JNK-dependent mechanism involving the mitochondrial pathway in NIH3T3 cells. Toxicol Lett 179:130–139

    Article  PubMed  CAS  Google Scholar 

  32. Carlson C, Hussain S, Schrand A, Braydich-Stollen K, Hess K, Jones R, Schlager J (2008) Unique cellular interaction of silver nanoparticles: Size-dependent generation of reactive oxygen species. J Phys Chem B 112:13608–13619

    Article  PubMed  CAS  Google Scholar 

  33. Braydich-Stollen L, Hussain S, Schlager J, Hofman M (2005) In vitro cytotoxicity of nanoparticles in mammalian germline stem cells. Toxicol Sci 88:412–419

    Article  Google Scholar 

  34. Panacek A, Kvitek L, Prucek R, Kolar M, Vecerova R, Pizurova N, Sharma V, Nevecna T, Zboril R (2006) Silver colloid nanoparticles: synthesis, characterization, and their antibacterial activity. J Phys Chem B 110:16248–16253

    Article  PubMed  CAS  Google Scholar 

  35. T. Habijan, O. Bremm, S. Esenwein, G. Muhr, M. Köller (2007), Influence of nickel ions on human multipotent mesenchymal stem cells, Mat.-wiss. u. Werkstofftech., 38

  36. Fritz E, Glant T, Vermes C, Jacobs J, Roebuck K (2002) Titanium particles induce the immediate early stress responsive chemokines IL-8 and MCP-1 in osteoblasts. J Orthop Res 20:490–498

    Article  PubMed  CAS  Google Scholar 

  37. Blain T, Rosier R, Puzas J, Looney R, Reynolds P, Reynolds S, O’Keefe R (1996) Increased levels of tumor necrosis factor-alpha and interleukin-6 protein and messenger RNA in human peripheral blood monocytes due to titantium particels. J Bone Joint Surg Am 78:1181–1192

    Google Scholar 

  38. Schmalz G, Schweikl H, Hiller K (2000) Release of prostaglandine E2, IL-6 and IL-8 from human oral epithelial culture models after exposure to compounds of dental materials. Eur J Oral Sci 108:442–448

    Article  PubMed  CAS  Google Scholar 

  39. Wataha J, Lockwood P, Schedle A, Noda M, Bouillaguet S (2002) Ag, Cu, Hg and Ni ions alter the metabolism of human monocytes during extended low-dose exposure. J Oral Rehabil 29:133–139

    Article  PubMed  CAS  Google Scholar 

  40. Wataha J, Lockwood P, Schedle A (2000) Effect of silver, copper, mercury, and nickel ions on cellular proliferation during extended, low-dose exposure. J Biomed Mater Res 52:360–364

    Article  PubMed  CAS  Google Scholar 

  41. Wagner M, Klein C, van Kooten T, Kirkpatrick C (1998) Mechanisms of cell activation by heavy metal ions. J Biomed Mater Res 42:443–452

    Article  PubMed  CAS  Google Scholar 

  42. Doty C, Tshikhudo R, Brust M, Fernig D (2005) Extremely stable water-soluble Ag nanoparticles. Chem Mater 17:4630–4635

    Article  CAS  Google Scholar 

  43. Moskovits M, Vlckova B (2005) Adsorbate-induced silver nanoparticle aggregation kinetics. J Phys Chem B 109:14755–14758

    Article  PubMed  CAS  Google Scholar 

  44. Peters T (1996) All About Albumin: Biochemistry, Genetics, and Medical Applications. ISBN:0-12-552110-3

Download references

Acknowledgments

Special thanks to the Deutsche Forschungsgemeinschaft (DFG) for financial support in the framework of the priority program NanoBioResponses (SPP 1313).

Author information

Authors and Affiliations

  1. Department of Surgery, Surgical Research, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany

    C. Greulich, G. Muhr & M. Köller

  2. Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen, Universitaetsstrasse 5-7, 45117, Essen, Germany

    S. Kittler & M. Epple

Authors
  1. C. Greulich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Kittler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Epple
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Muhr
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Köller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Greulich.

Additional information

“Best of Abstracts – Chirurgisches Forum 2009, Deutsche Gesellschaft für Chirurgie”

Rights and permissions

Reprints and permissions

About this article

Cite this article

Greulich, C., Kittler, S., Epple, M. et al. Studies on the biocompatibility and the interaction of silver nanoparticles with human mesenchymal stem cells (hMSCs). Langenbecks Arch Surg 394, 495–502 (2009). https://doi.org/10.1007/s00423-009-0472-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00423-009-0472-1

Keywords

Search

Navigation