Skip to main content
SpringerLink
Log in

Effect of gold nanoparticles on adipogenic differentiation of human mesenchymal stem cells

  • Research Paper
  • Published:
Journal of Nanoparticle Research Aims and scope Submit manuscript

Abstract

Gold nanoparticles are very attractive for biomedical products. However, there is a serious lack of information concerning the biological activity of nanosized gold in human tissue cells. An influence of nanoparticles on stem cells might lead to unforeseen consequences to organ and tissue functions as long as all cells arising from the initial stem cell might be subsequently damaged. Therefore the effect of negatively charged gold nanoparticles (9 and 95 nm), which are certified as reference material for preclinical biomedical research, on the adipogenic differentiation of human mesenchymal stem cells (hMSCs) is investigated here. Bone marrow hMSCs are chosen as differentiation model since bone marrow hMSCs are well characterized and their differentiation into the adipogenic lineage shows clear and easily detectable differentiation. In this study effects of gold nanoparticles on adipogenic differentiation are analyzed regarding fat storage and mitochondrial activity after different exposure times (4–21 days). Using time lapse microscopy the differentiation progress under chronically gold nanoparticle treatment is continuously investigated. In this preliminary study, chronically treatment of adipogenic differentiating hMSCs with gold nanoparticles resulted in a reduced number and size of lipid vacuoles and reduced mitochondrial activity depending on the applied concentration and the surface charge of the particles.

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
Fig. 6
Fig. 7
Fig 8
Fig. 9

Similar content being viewed by others

References

  • Alkilany AM, Nagaria PK, Hexel CR, Shaw TJ, Murphy CJ, Wyatt MD (2009) Cellular uptake and cytotoxicity of gold nanorods: molecular origin of cytotoxicity and surface effects. Small 5:701–708. doi:10.1002/smll.200801546

    Article  CAS  Google Scholar 

  • Arnida A, Malugin A, Ghandehari H (2010) Cellular uptake and toxicity of gold nanoparticles in prostate cancer cells: a comparative study of rods and spheres. J Appl Toxicol 30:212–217. doi:10.1002/jat.1486

    CAS  Google Scholar 

  • Boisselier E, Astruc D (2009) Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. Chem Soc Rev 38:1759–1782. doi:10.1039/B806051G

    Article  CAS  Google Scholar 

  • Brandenberger C, Rothen-Rutishauser B, Mühlfeld C, Schmid O, Ferron GA, Maier KL, Gehr P, Lenz AG (2010) Effects and uptake of gold nanoparticles deposited at the air-liquid interface of a human epithelial airway model. Toxicol Appl Pharmacol 242:56–65. doi:10.1016/j.taap.2009.09.014

    Article  CAS  Google Scholar 

  • Brasaemle DL (2007) The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis. J Lipid Res 48:2547–2559. doi:10.1194/jlr.R700014-JLR200

    Article  CAS  Google Scholar 

  • Braydich-Stolle L, Hussain S, Schlager JJ, Hofmann MC (2005) In vitro cytotoxicity of nanoparticles in mammalian germline stem cells. Toxicol Sci 88:412–419. doi:10.1093/toxsci/kfi256

    Article  CAS  Google Scholar 

  • Brown CL, Whitehouse MW, Tiekink ER, Bushell GR (2008) Colloidal metallic gold is not bio-inert. Inflammopharmacology 16:133–137

    Article  CAS  Google Scholar 

  • Connor EE, Mwamuka J, Gole A, Murphy CJ, Wyatt MD (2005) Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small 1:325–327. doi:10.1002/smll.200400093

    Article  CAS  Google Scholar 

  • De Jong WH, Hagens WI, Krystek P, Burger MC, Sips AJAM, Geertsma RE (2008) Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. Biomaterials 29:1912–1919. doi:10.1016/j.biomaterials.2007.12.037

    Article  Google Scholar 

  • Di Guglielmo C, López DR, De Lapuente J, Mallafre JML, Suàrez MB (2010) Embryotoxicity of cobalt ferrite and gold nanoparticles: a first in vitro approach reproductive toxicology. Reprod Toxicol 30:271–276. doi:10.1016/j.reprotox.2010.05.001

    Article  CAS  Google Scholar 

  • Diegoli S, Manciulea AL, Begum S, Jones IP, Lead JR, Preece JA (2008) Interaction between manufactured gold nanoparticles and naturally occurring organic macromolecules. Sci Total Environ 4:51–61. doi:10.1016/j.scitotenv.2008.04.023

    Google Scholar 

  • Ehrenberg MS, Friedman AE, Finkelstein JN, Oberdörster G, McGrath JL (2009) The influence of protein adsorption on nanoparticle association with cultured endothelial cells. Biomaterials 30:603–610. doi:10.1016/j.biomaterials.2008.09.050

    Article  CAS  Google Scholar 

  • Fan JH, Huang WI, Li WT, Yeh JM (2009) Biocompatibility study of gold nanoparticles to human cells. ICBME Proceedings 23:870–873

    Google Scholar 

  • Frens G (1973) Controlled nucleation for the regulation of the particle size in monodisperse gold suspensions. Nature 241:20–22. doi:10.1038/physci241020a0

    CAS  Google Scholar 

  • Fröhlich E, Samberger C, Kueznik T, Absenger M, Roblegg E, Zimmer A, Pieber TR (2009) Cytotoxicity of nanoparticles independent from oxidative stress. J Toxicol Sci 34:363–375

    Article  Google Scholar 

  • Goodman CM, McCusker CD, Yilmaz T, Rotello VM (2004) Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. Bioconjug Chem 15:897–900. doi:10.1021/bc049951i

    Article  CAS  Google Scholar 

  • Hackenberg S, Scherzed A, Kessler M, Hummel S, Technau A, Froelich A, Ginzkey C, Koehler C, Hagen R, Kleinsasser N (2010) Silver nanoparticles: evaluation of DNAdamage, toxicity and functional impairment in human mesenchymal stem cells. Toxicol Lett 201:27–33. doi:10.1016/j.toxlet.2010.12.001

    Article  Google Scholar 

  • Hainfeld JF, Slatkin DN, Focella TM, Smilowitz HM (2006) Gold nanoparticles: a new X-ray contrast agent. Br J Radiol 79:248–253. doi:10.1259/bjr/13169882

    Article  CAS  Google Scholar 

  • Hauck TS, Ghazani AA, Chan WCW (2008) Assessing the effect of surface chemistry on gold nanorod uptake, toxicity, and gene expression in mammalian cells. Small 4:153–159. doi:10.1002/smll.200700217

    Article  CAS  Google Scholar 

  • Hoet P, Brüske-Hohlfeld I, Salata O (2004) Nanoparticles—known and unknown health risks. J Nanobiotechnology 2:1–15. doi:10.1186/1477-3155-2-12

    Article  Google Scholar 

  • Katsen AD, Vollmar B, Mestres-Ventura P, Menger MD (1998) Cell surface and nuclear changes during TNF-alpha-induced apoptosis in WEHI 164 murine fibrosarcoma cells. A correlative light, scanning, and transmission electron microscopical study. Virchows Arch 433:75–83. doi:10.1007/s004280050219

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  • Kong T, Zeng J, Wang X, Yang X, Yang J, McQuarrie S, McEwan A, Roa W, Chen J, Xing JZ (2008) Enhancement of radiation cytotoxicity in breast-cancer cells by localized attachment of gold nanoparticles. Small 4:1537–1543. doi:10.1002/smll.200700794

    Article  CAS  Google Scholar 

  • Kuo WS, Chang CN, Chang YT, Yang MH, Chien YH, Chen SJ, Yeh CS (2010) Gold nanorods in photodynamic therapy, as hyperthermia agents, and in near-infrared optical imaging. Angew Chem Int Ed 49:2711–2715. doi:10.1002/anie.200906927

    CAS  Google Scholar 

  • Lillie RD, Ashburn LL (1943) Supersaturated solutions of fat stains in dilute isopropanol for demonstration of acute fatty degeneration not shown by Herxheimer’s technique. Arch Pathol 36:432–440

    Google Scholar 

  • Liu DD, Zhang JC, Yi CQ, Yang (2010) The effects of gold nanoparticles on the proliferation, differentiation, and mineralization function of MC3T3-E1 cells in vitro. Chinese Sci Bull 55:1013–1019. doi:10.1007/s11434-010-0046-1

    Google Scholar 

  • Male KB, Lanchance B, Hrapovic S, Sunahara G, Loung JHT (2008) Assessment of cytotoxicity of quantum dots and gold nanoparticles using cell-based impedance spectroscopy. Anal Chem 80:5487–5493. doi:10.1021/ac8004555

    Article  CAS  Google Scholar 

  • Murphy CJ, Gole AM, Stone JW, Sisco PN, Alkilany AM, Goldsmith EC, Baxter SC (2008) Gold nanoparticles in biology: beyond toxicity to cellular imaging. Acc Chem Res 41:1721–1730

    Article  CAS  Google Scholar 

  • NanoTech Gold News (2008) BBI Partners with NIST to develop the ‘gold standard’ in nanoparticles. Gold Bulletin 41(1):NTGN1–NTGN4. doi:10.1007/BF03215628

    Google Scholar 

  • Oberdörster G, Oberdörster E, Oberdörster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–839. doi:10.1289/ehp.7339

    Article  Google Scholar 

  • Pan Y, Neuss S, Leifert A, Fischler M, Wen F, Simon U, Schmid G, Brandau W, Jahnen-Dechent W (2007) Size-dependent cytotoxicity of gold nanoparticles. Small 3:1941–1949. doi:10.1002/smll.200700378

    Article  CAS  Google Scholar 

  • Pan Y, Leifert A, Ruau D, Neuss S, Bornemann J, Schmid G, Brandau W, Simon U, Jahnen-Dechent W (2009) Gold nanoparticles of diameter 1.4 nm trigger necrosis by oxidative stress and mitochondrial damage. Small 5:2067–2076. doi:10.1002/smll.200900466

    Article  CAS  Google Scholar 

  • Pernodet N, Fang X, Sun Y, Bakhtina A, Ramakrishnan A, Sokolov J, Ulman A, Rafailovich M (2006) Adverse effects of citrate/gold nanoparticles on human dermal fibroblasts. Small 2:766–773. doi:10.1002/smll.200500492

    Article  CAS  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147. doi:10.1126/science.284.5411.143

    Article  CAS  Google Scholar 

  • Rush GF, Smith PF, Alberts DW, Mirabelli K, Snyder SM, Crooke ST, Sowinski J, Jones H, Bugelski PJ (1987) The mechanism of acute cytotoxicity of triethylphosphine gold(I) complexes. I. characterization of triethylphosphine gold chloride-induced biochemical and morphological changes in isolated hepatocytes. Toxicol Appl Pharmaco 90:377–390

    Article  CAS  Google Scholar 

  • Schaeublin NM, Braydich-Stolle LK, Schrand AM, Miller JM, Hutchison J, Schlager JJ, Hussain SM (2011) Surface charge of gold nanoparticles mediates mechanism of toxicity. Nanoscale 3:410–420. doi:10.1039/c0nr00478b

    Article  CAS  Google Scholar 

  • Sereemaspun A, Rojanathanes R, Wiwanitkit V (2008) Effect of gold nanoparticle on renal cell: an implication for exposure risk. Ren Fail 30:323–325. doi:10.1080/08860220701860914

    Article  CAS  Google Scholar 

  • Wigglesworth VB (1975) Lipid staining for electron microscopy: a new method. J Cell Sci 19:425–437

    CAS  Google Scholar 

  • Yen HJ, Hsu SH, Tsai CL (2009) Cytotoxicity and immunological response of gold and silver nanoparticles of different sizes. Small 5:1553–1561. doi:10.1002/smll.200900126

    Article  CAS  Google Scholar 

  • Yi C, Liu D, Fong CC, Zhang J, Yang M (2010) Gold nanoparticles promote osteogenic differentiation of mesenchymal stem cells through p38 MAPK pathway. ACS Nano 4:6439–6448. doi:10.1021/nn101373r

    Article  CAS  Google Scholar 

  • Zhu L, Chang DW, Dai L, Hong Y (2007) DNA damage induced by multiwalled carbon nanotubes in mouse embryonic stem cells. Nano Lett 7:3592–3597. doi:10.1021/nl071303v

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dipl.-Chem. Andreas Henkel (Johannes Gutenberg University Mainz, Institute for Physical Chemistry, Mainz, Germany) for his assistance with TEM and Norbert Pütz (Saarland University.

Department of Anatomy and Cell Biology, Germany) and for his help with the SEM. We also thank Yulia Zaytseva for her technical assistance in the electron microscopy study.

Author information

Authors and Affiliations

  1. Department of Cell Biology & Applied Virology, Fraunhofer Institute for Biomedical Engineering, Ensheimer Straße 48, 66386, St. Ingbert, Germany

    Yvonne Kohl, Erwin Gorjup & Hagen von Briesen

  2. Department of Biophysics & Cryotechnology, Fraunhofer Institute for Biomedical Engineering, Ensheimer Straße 48, 66386, St. Ingbert, Germany

    Alisa Katsen-Globa

  3. Institute of Molecular Biosciences, University of Frankfurt, Siesmayerstrasse 70, 60323, Frankfurt, Germany

    Claudia Büchel

  4. Vanguard AG, Landsberger Straße 219, 12623, Berlin, Germany

    Hagen Thielecke

Authors
  1. Yvonne Kohl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erwin Gorjup
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alisa Katsen-Globa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Claudia Büchel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hagen von Briesen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hagen Thielecke
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hagen von Briesen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kohl, Y., Gorjup, E., Katsen-Globa, A. et al. Effect of gold nanoparticles on adipogenic differentiation of human mesenchymal stem cells. J Nanopart Res 13, 6789–6803 (2011). https://doi.org/10.1007/s11051-011-0587-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11051-011-0587-5

Keywords

Search

Navigation