Log in

Carboxylated Superparamagnetic Iron Oxide Particles Label Cells Intracellularly Without Transfection Agents

  • Research Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Cell labeling by superparamagnetic iron oxide particles (SPIO) has emerged as a potentially powerful tool to monitor trafficking of transplanted cells by magnetic resonance tomography, e.g., in studies for tissue repair. However, intracellular labeling is mostly achieved by transfection agents not approved for clinical use. In this work, the feasibility and efficiency of labeling human mesenchymal stem cells (MSC) and HeLa cells with two commercially available SPIOs (Resovist® and Feridex®) without transfection agents was evaluated. In both cell types, Resovist® without a transfection agent was more efficiently taken up than Feridex®. Increasing the concentration of Resovist® can yield similar amounts of iron in cells as SPIOs with transfection agents. This offers the opportunity to omit transfection agents from the labeling protocol when Resovist® is used. Intracellular localization of the contrast agents is found by light microscopy and confirmed by electron microscopy. Coagulation of the SPIO nanoparticles, which is problematic for the quantification of the intracellular iron content, was observed and analyzed with a fluorescent activated cell sorter. As Resovist® consists of a carboxydextran shell in contrast to Feridex® which is composed of a dextran shell, we synthesized fluorescent polymeric nanoparticles as model systems with different amounts of carboxyl groups on the surface by the miniemulsion process. A steady increase in uptake of nanoparticles was detected with a higher density of carboxyl groups showing the relevance of charged groups as in the case of Resovist®. Aggregation of these polymeric nanoparticles was not found.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Thorne SH, Negrin RS, Contag CH (2006) Synergistic antitumor effects of immune cell-viral biotherapy. Science 311:1780–1784

    Article  PubMed  CAS  Google Scholar 

  2. Contag CH (2006) Molecular imaging using visible light to reveal biological changes in the brain. Neuroimaging Clin N Am 16:633–654

    Article  PubMed  Google Scholar 

  3. Hofmann M, Wollert KC, Meyer GP et al (2005) Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation 111:2198–2202 Epub 2005 Apr 2125

    Article  PubMed  Google Scholar 

  4. Michalet X, Pinaud FF, Bentolila LA et al (2005) Quantum dots for live cells, in vivo imaging, and diagnostics. Science 307:538–544

    Article  PubMed  CAS  Google Scholar 

  5. Scarff M, Arnold SA, Harvey LM et al (2006) Near infrared spectroscopy for bioprocess monitoring and control: current status and future trends. Crit Rev Biotechnol 26:17–39

    Article  PubMed  CAS  Google Scholar 

  6. Giesel FL, Stroick M, Griebe M et al (2006) Gadofluorine m uptake in stem cells as a new magnetic resonance imaging tracking method: an in vitro and in vivo study. Invest Radiol 41:868–873

    Article  PubMed  CAS  Google Scholar 

  7. Kraitchman DL, Heldman AW, Atalar E et al (2003) In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction. Circulation 107:2290–2293 Epub 2003 May 2295

    Article  PubMed  Google Scholar 

  8. Frank JA, Zywicke H, Jordan EK et al (2002) Magnetic intracellular labeling of mammalian cells by combining (FDA-approved) superparamagnetic iron oxide MR contrast agents and commonly used transfection agents. Acad Radiol 9:S484–487

    Article  PubMed  Google Scholar 

  9. Montet-Abou K, Montet X, Weissleder R et al (2005) Transfection agent induced nanoparticle cell loading. Mol Imaging 4:165–171

    PubMed  Google Scholar 

  10. Arbab AS, Yocum GT, Kalish H et al (2004) Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI. Blood 104:1217–1223 Epub 2004 Apr 1220

    Article  PubMed  CAS  Google Scholar 

  11. Arbab AS, Yocum GT, Wilson LB et al (2004) Comparison of transfection agents in forming complexes with ferumoxides, cell labeling efficiency, and cellular viability. Mol Imaging 3:24–32

    Article  PubMed  CAS  Google Scholar 

  12. Ju S, Teng G, Zhang Y et al (2006) In vitro labeling and MRI of mesenchymal stem cells from human umbilical cord blood. Magn Reson Imaging 24:611–617 Epub 2006 Feb 2017

    Article  PubMed  Google Scholar 

  13. Hunter AC (2006) Molecular hurdles in polyfectin design and mechanistic background to polycation induced cytotoxicity. Adv Drug Deliv Rev 58:1523–1531

    Article  PubMed  CAS  Google Scholar 

  14. Symonds P, Murray JC, Hunter AC et al (2005) Low and high molecular weight poly(L-lysine)s/poly(L-lysine)-DNA complexes initiate mitochondrial-mediated apoptosis differently. FEBS Lett 579:6191–6198

    Article  PubMed  CAS  Google Scholar 

  15. de Vries IJ, Lesterhuis WJ, Barentsz JO et al (2005) Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol 23:1407–1413 Epub 2005 Oct 1430

    Article  PubMed  Google Scholar 

  16. Zimmet J, Hare J (2005) Emerging role for bone marrow derived mesenchymal stem cells in myocardial regenerative therapy. Basic Res Cardiol 100:471–481

    Article  PubMed  CAS  Google Scholar 

  17. Kemp K, Hows J, Donaldson C (2005) Bone marrow-derived mesenchymal stem cells. Leuk Lymphoma 46:1531–1544

    Article  PubMed  Google Scholar 

  18. Noel D, Djouad F, Jorgense C (2002) Regenerative medicine through mesenchymal stem cells for bone and cartilage repair. Curr Opin Investig Drugs 3:1000–1004

    PubMed  Google Scholar 

  19. Landfester K (2006) Synthesis of colloidal particles in miniemulsions. Ann Rev Mat Res 36:231–279

    Article  CAS  Google Scholar 

  20. Holzapfel V, Musyanovych A, Landfester K et al (2006) Preparation of fluorescent carboxyl and amino functionalized polystyrene particles by minie-mulsion polymerization as markers for cells. J Phys Condens Matter 18:S2581–S2594

    Article  CAS  Google Scholar 

  21. Eisenstein M (2006) Cell sorting: divide and conquer. Nature 441:1179–1185

    Article  PubMed  Google Scholar 

  22. Pittenger MF, Martin BJ (2004) Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 95:9–20

    Article  PubMed  CAS  Google Scholar 

  23. Holzapfel V, Lorenz M, Weiss CK et al (2006) Synthesis and biomedical applications of functionalized fluorescent and magnetic dual reporter nanoparticles as obtained in the miniemulsion process. J Phys Condens Matter 18:S2581–S2594

    Article  CAS  Google Scholar 

  24. Heyn C, Bowen CV, Rutt BK et al (2005) Detection threshold of single SPIO-labeled cells with FIESTA. Magn Reson Med 53:312–320

    Article  PubMed  Google Scholar 

  25. Dahnke H, Schaeffter T (2005) Limits of detection of SPIO at 3.0 T using T2 relaxometry. Magn Reson Med 53:1202–1206

    Article  PubMed  CAS  Google Scholar 

  26. Sun R, Dittrich J, Le-Huu M et al (2005) Physical and biological characterization of superparamagnetic iron oxide- and ultrasmall superparamagnetic iron oxide-labeled cells: a comparison. Invest Radiol 40:504–513

    Article  PubMed  Google Scholar 

  27. Metz S, Bonaterra G, Rudelius M et al (2004) Capacity of human monocytes to phagocytose approved iron oxide MR contrast agents in vitro. Eur Radiol 14:1851–1858 Epub 2004 Jul 1813

    Article  PubMed  Google Scholar 

  28. Leuschner C, Kumar CS, Hansel W et al (2006) LHRH-conjugated magnetic iron oxide nanoparticles for detection of breast cancer metastases. Breast Cancer Res Treat 99:163–176 Epub 2006 Jun 2003

    Article  PubMed  CAS  Google Scholar 

  29. Warren RA, Green FA, Enns CA (1997) Saturation of the endocytic pathway for the transferrin receptor does not affect the endocytosis of the epidermal growth factor receptor. J Biol Chem 272:2116–2121

    Article  PubMed  CAS  Google Scholar 

  30. Lorenz MR, Holzapfel V, Musyanovych A et al (2006) Uptake of functionalized, fluorescent-labeled polymeric particles in different cell lines and stem cells. Biomaterials 27:2820–2828 Epub 2006 Jan 2823

    Article  PubMed  CAS  Google Scholar 

  31. Fattal E, Couvreur P, Dubernet C (2004) “Smart” delivery of antisense oligonucleotides by anionic pH-sensitive liposomes. Adv Drug Deliv Rev 56:931–946

    Article  PubMed  CAS  Google Scholar 

  32. Freulon I, Roche AC, Monsigny M et al (2001) Delivery of oligonucleotides into mammalian cells by anionic peptides: comparison between monomeric and dimeric peptides. Biochem J 354:671–679

    Article  PubMed  CAS  Google Scholar 

  33. Bulte JW, Douglas T, Witwer B et al (2001) Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat Biotechnol 19:1141–1147

    Article  PubMed  CAS  Google Scholar 

  34. Stebelska K, Dubielecka PM, Sikorski AF (2005) The effect of PS content on the ability of natural membranes to fuse with positively charged liposomes and lipoplexes. J Membr Biol 206:203–214

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

In the Institute of Clinical Transfusion Medicine and Immunogenetics, Ulm, we would like to thank K. Fuchs, L. Ermisch, G. Baur and T. Becker for their assistance with the MSC cell cultures and in the Central Facility for Electron Microscopy G. Kräutle, E. Schmidt and R. Weih for their expert technical assistance with the TEM and SEM. This work was supported by a Bausteinförderung from the University Clinic of Ulm (P.871) and the German Research Foundation (DFG; LA1013-3 and MA3271-1).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Volker Mailänder.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM Fig. 1

(GIF 1.51 kb)

ESM Fig. 2

(GIFF 22.4 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mailänder, V., Lorenz, M.R., Holzapfel, V. et al. Carboxylated Superparamagnetic Iron Oxide Particles Label Cells Intracellularly Without Transfection Agents. Mol Imaging Biol 10, 138–146 (2008). https://doi.org/10.1007/s11307-007-0130-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-007-0130-3

Key words

Navigation