Skip to main content
SpringerLink
Log in

Magnetic resonance imaging probes for labeling of chondrocyte cells

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

Recent progress in cell therapy research has raised the need for non-invasive monitoring of transplanted cells. Magnetic resonance imaging (MRI) of superparamagnetic iron oxide (SPIO) labeled cells have been widely used for high resolution monitoring of the biodistribution of cells after transplantation. Here we report that self-assembly of amphiphilic polyethylenimine (PEI)/SPIO nanocomposites can lead to the formation of ultrasensitive MRI probes, which can be used to label chondrocyte cells with good biocompatibility. The labeled cells display strong signal contrast compared to unlabeled ones in a clinical MRI scanner. This probe may be useful for noninvasive MR tracking of implanted cells for tissue regeneration.

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

Similar content being viewed by others

References

  1. Kurozumi K, Nakamura K, Tamiya T, Kawano Y, Ishii K, Kobune M, Hirai S, Uchida H, Sasaki K, Ito Y, Kato K, Honmou O, Houkin K, Date I, Hamada H. Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model. Mol Ther. 2005;11:96–104.

    Article  CAS  Google Scholar 

  2. Satake K, Lou J, Lenke LG. Migration of mesenchymal stem cells through cerebrospinal fluid into injured spinal cord tissue. Spine (Phila Pa 1976). 2004;29:1971–9.

    Google Scholar 

  3. Trippel SB. Autologous chondrocyte transplantation. N Engl J Med. 1995;332:539–40.

    Article  CAS  Google Scholar 

  4. van Osch GJ, Brittberg M, Dennis JE, Bastiaansen-Jenniskens YM, Erben RG, Konttinen YT, Luyten FP. Cartilage repair: past and future–lessons for regenerative medicine. J Cell Mol Med. 2009;13:792–810.

    Article  Google Scholar 

  5. Weissleder R, Mahmood U. Molecular imaging. Radiology. 2001;219:316–33.

    CAS  Google Scholar 

  6. Schroeder T. Imaging stem-cell-driven regeneration in mammals. Nature. 2008;453:345–51.

    Article  CAS  Google Scholar 

  7. Smith BR, Johnson GA, Groman EV, Linney E. Magnetic resonance microscopy of mouse embryos. Proc Natl Acad Sci USA. 1994;91:3530–3.

    Article  CAS  Google Scholar 

  8. Bulte JW, Kraitchman DL. Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed. 2004;17:484–99.

    Article  CAS  Google Scholar 

  9. Jacobs RE, Fraser SE. Magnetic resonance microscopy of embryonic cell lineages and movements. Science. 1994;263:681–4.

    Article  CAS  Google Scholar 

  10. Frank JA, Zywicke H, Jordan EK, Mitchell J, Lewis BK, Miller B, Bryant LH Jr, Bulte, JW. Magnetic intracellular labeling of mammalian cells by combining (FDA-approved) superparamagnetic iron oxide MR contrast agents and commonly used transfection agents. Acad Radiol. 2002; 9 Suppl 2:S484–7.

    Article  Google Scholar 

  11. Lu CW, Hung Y, Hsiao JK, Yao M, Chung TH, Lin YS, Wu SH, Hsu SC, Liu HM, Mou CY, Yang CS, Huang DM, Chen YC. Bifunctional magnetic silica nanoparticles for highly efficient human stem cell labeling. Nano Lett. 2007;7:149–54.

    Article  CAS  Google Scholar 

  12. Smirnov P, Lavergne E, Gazeau F, Lewin M, Boissonnas A, Doan BT, Gillet B, Combadiere C, Combadiere B, Clement O. In vivo cellular imaging of lymphocyte trafficking by MRI: a tumor model approach to cell-based anticancer therapy. Magn Reson Med 2006;56:498–508.

    Article  CAS  Google Scholar 

  13. Ramaswamy S, Greco JB, Uluer MC, Zhang Z, Fishbein KW, Spencer RG. Magnetic resonance imaging of chondrocytes labeled with superparamagnetic iron oxide nanoparticles in tissue-engineered cartilage. Tissue Eng Part A. 2009;15:3899–910.

    Article  CAS  Google Scholar 

  14. Li Z, Suzuki Y, Huang M, Cao F, Xie X, Connolly AJ, Yang PC, Wu JC. Comparison of reporter gene and iron particle labeling for tracking fate of human embryonic stem cells and differentiated endothelial cells in living subjects. Stem Cells. 2008;26:864–73.

    Article  CAS  Google Scholar 

  15. Heymer A, Haddad D, Weber M, Gbureck U, Jakob PM, Eulert J, Noth U. Iron oxide labelling of human mesenchymal stem cells in collagen hydrogels for articular cartilage repair. Biomaterials. 2008;29:1473–83.

    Article  CAS  Google Scholar 

  16. Sun S. Recent advances in chemical synthesis, self-assembly, and applications of FePt nanoparticles. Adv Mater. 2006;18:393–403.

    Article  CAS  Google Scholar 

  17. Metz S, Bonaterra G, Rudelius M, Settles M, Rummeny EJ, Daldrup-Link HE. Capacity of human monocytes to phagocytose approved iron oxide MR contrast agents in vitro. Eur Radiol. 2004;14:1851–8.

    Article  Google Scholar 

  18. Ahrens ET, Feili-Hariri M, Xu H, Genove G, Morel PA. Receptor-mediated endocytosis of iron-oxide particles provides efficient labeling of dendritic cells for in vivo MR imaging. Magn Reson Med. 2003;49:1006–13.

    Article  CAS  Google Scholar 

  19. Arbab AS, Yocum GT, Kalish H, Jordan EK, Anderson SA, Khakoo AY, Read EJ, Frank JA. Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI. Blood. 2004;104:1217–23.

    Article  CAS  Google Scholar 

  20. Babic M, Horak D, Trchova M, Jendelova P, Glogarova K, Lesny P, Herynek V, Hajek M, Sykova E. Poly(l-lysine)-modified iron oxide nanoparticles for stem cell labeling. Bioconjug Chem. 2008;19:740–50.

    Article  CAS  Google Scholar 

  21. Yeh TC, Zhang W, Ildstad ST, Ho C. In vivo dynamic MRI tracking of rat T-cells labeled with superparamagnetic iron-oxide particles. Magn Reson Med. 1995;33:200–8.

    Article  CAS  Google Scholar 

  22. Zhang C, Jugold M, Woenne EC, Lammers T, Morgenstern B, Mueller MM, Zentgraf H, Bock M, Eisenhut M, Semmler W, Kiessling F. Specific targeting of tumor angiogenesis by RGD-conjugated ultrasmall superparamagnetic iron oxide particles using a clinical 1.5-T magnetic resonance scanner. Cancer Res. 2007;67:1555–62.

    Article  CAS  Google Scholar 

  23. Wang Z, Liu G, Sun J, Wu B, Gong Q, Song B, Ai H, Gu Z. Self-assembly of magnetite nanocrystals with amphiphilic polyethylenimine: structures and applications in magnetic resonance imaging. J Nanosci Nanotechnol. 2009;9:378–85.

    Article  CAS  Google Scholar 

  24. Lu J, Ma S, Sun J, Xia C, Liu C, Wang Z, Zhao X, Gao F, Gong Q, Song B, Shuai X, Ai H, Gu Z. Manganese ferrite nanoparticle micellar nanocomposites as MRI contrast agent for liver imaging. Biomaterials. 2009;30:2919–28.

    Article  CAS  Google Scholar 

  25. Ai H, Flask C, Weinberg B, Shuai X, Pagel M, Farrell D, Duerk J, Gao J. Magnetite-loaded polymeric micelles as ultrasensitive magnetic resonance probes. Adv Mater. 2005;17:1949–52.

    Article  CAS  Google Scholar 

  26. Zheng L, Sun J, Chen X, Wang G, Jiang B, Fan H, Zhang X. In vivo cartilage engineering with collagen hydrogel and allogenous chondrocytes after diffusion chamber implantation in immunocompetent host. Tissue Eng Part A. 2009;15:2145–53.

    Article  CAS  Google Scholar 

  27. Liu G, Tian J, Liu C, Ai H, Gu Z, Gou J, Mo X. Cell labeling efficiency of layer-by-layer self-assembly modified silica nanoparticles. J Mater Res. 2009;24:1317–21.

    Article  CAS  Google Scholar 

  28. Anderson SA, Glod J, Arbab AS, Noel M, Ashari P, Fine HA, Frank JA. Noninvasive MR imaging of magnetically labeled stem cells to directly identify neovasculature in a glioma model. Blood. 2005;105:420–5.

    Article  CAS  Google Scholar 

  29. Hill JM, Dick AJ, Raman VK, Thompson RB, Yu ZX, Hinds KA, Pessanha BS, Guttman MA, Varney TR, Martin BJ, Dunbar CE, McVeigh ER, Lederman RJ. Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells. Circulation. 2003;108:1009–14.

    Article  Google Scholar 

  30. Kircher MF, Allport JR, Graves EE, Love V, Josephson L, Lichtman AH, Weissleder R. In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic T-lymphocyte trafficking to tumors. Cancer Res. 2003;63:6838–46.

    CAS  Google Scholar 

  31. Chung TH, Wu SH, Yao M, Lu CW, Lin YS, Hung Y, Mou CY, Chen YC, Huang DM. The effect of surface charge on the uptake and biological function of mesoporous silica nanoparticles in 3T3–L1 cells and human mesenchymal stem cells. Biomaterials. 2007;28:2959–66.

    Article  CAS  Google Scholar 

  32. Thorek DL, Tsourkas A. Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cells. Biomaterials. 2008;29:3583–90.

    Article  CAS  Google Scholar 

  33. Farrell E, Wielopolski P, Pavljasevic P, Kops N, Weinans H, Bernsen MR, van Osch GJ. Cell labelling with superparamagnetic iron oxide has no effect on chondrocyte behaviour. Osteoarthr Cartil. 2009;17:961–7.

    Article  CAS  Google Scholar 

  34. Stoddart MJ, Grad S, Eglin D, Alini M. Cells and biomaterials in cartilage tissue engineering. Regen Med 2009;4:81–98.

    Article  CAS  Google Scholar 

  35. Pawelczyk E, Arbab AS, Pandit S, Hu E, Frank JA. Expression of transferrin receptor and ferritin following ferumoxides-protamine sulfate labeling of cells: implications for cellular magnetic resonance imaging. NMR Biomed. 2006;19:581–92.

    Article  CAS  Google Scholar 

  36. Aisen P, Enns C, Wessling-Resnick M. Chemistry and biology of eukaryotic iron metabolism. Int J Biochem Cell Biol. 2001;33:940–59.

    Article  CAS  Google Scholar 

Download references

Acknowledgment

The work was supported by Program for New Century Excellent Talents in University (NCET-06-0781), Distinguished Young Scholars Project of Sichuan Province (06ZQ026-007), and National Natural Science Foundation of China (20974065, 50603015, and 50830107).

Author information

Authors and Affiliations

  1. National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China

    Gang Liu, Zhiyong Wang, Fei Lv, Hua Ai & Zhongwei Gu

  2. Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China

    Chunchao Xia, Fabao Gao, Qiyong Gong, Bin Song & Hua Ai

  3. Institute of Materia Medica and Department of Pharmacology, North Sichuan Medical College, Nanchong, Sichuan, 637007, China

    Gang Liu

  4. Sichuan Key Laboratory of Medical Imaging, Department of Radiology, North Sichuan Medical College, Nanchong, 637007, China

    Gang Liu

Authors
  1. Gang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chunchao Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhiyong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fei Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fabao Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qiyong Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bin Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hua Ai
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Zhongwei Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hua Ai.

Additional information

Gang Liu and Chunchao Xia contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, G., Xia, C., Wang, Z. et al. Magnetic resonance imaging probes for labeling of chondrocyte cells. J Mater Sci: Mater Med 22, 601–606 (2011). https://doi.org/10.1007/s10856-010-4227-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-010-4227-x

Keywords

Search

Navigation