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Controllable labelling of stem cells with a novel superparamagnetic iron oxide–loaded cationic nanovesicle for MR imaging

  • Molecular Imaging
  • Published:
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Abstract

Objective

To investigate the feasibility of highly efficient and controllable stem cell labelling for cellular MRI.

Methods

A new class of cationic, superparamagnetic iron oxide nanoparticle (SPION)-loaded nanovesicles was synthesised to label rat bone marrow mesenchymal stem cells without secondary transfection agents. The optimal labelling conditions and controllability were assessed, and the effect of labelling on cell viability, proliferation activity and multilineage differentiation was determined. In 18 rats, focal ischaemic cerebral injury was induced and the rats randomly injected with 1 × 106 cells labelled with 0-, 8- or 20-mV nanovesicles (n = 6 each). In vivo MRI was performed to follow grafted cells in contralateral striata, and results were correlated with histology.

Results

Optimal cell labelling conditions involved a concentration of 3.15 μg Fe/mL nanovesicles with 20-mV positive charge and 1-h incubation time. Labelling efficiency showed linear change with an increase in the electric potentials of nanovesicles. Labelling did not affect cell viability, proliferation activity or multilineage differentiation capacity. The distribution and migration of labelled cells could be detected by MRI. Histology confirmed that grafted cells retained the label and remained viable.

Conclusion

Stem cells can be effectively and safely labelled with cationic, SPION-loaded nanovesicles in a controllable way for cellular MRI.

Key Points

Stem cells can be effectively labelled with cationic, SPION-loaded nanovesicles.

Labelling did not affect cell viability, proliferation or differentiation.

Cellular uptake of SPION could be controlled using cationic nanovesicles.

Labelled cells could migrate along the corpus callosum towards cerebral infarction.

The grafted, labelled cells retained the label and remained viable.

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References

  1. Mimeault M, Hauke R, Batra SK (2007) Stem cells: a revolution in therapeutics—recent advances in stem cell biology and their therapeutic applications in regenerative medicine and cancer therapies. Clin Pharmacol Ther 82:252–264

    Article  PubMed  CAS  Google Scholar 

  2. Mimeault M, Batra SK (2006) Concise review: recent advances on the significance of stem cells in tissue regeneration and cancer therapies. Stem Cells 24:2319–2345

    Article  PubMed  CAS  Google Scholar 

  3. Lee Z, Dennis JE, Gerson SL (2008) Imaging stem cell implant for cellular-based therapies. Exp Biol Med (Maywood) 233:930–940

    Article  CAS  Google Scholar 

  4. Walczak P, Bulte JW (2007) The role of noninvasive cellular imaging in developing cell-based therapies for neurodegenerative disorders. Neurodegener Dis 4:306–313

    Article  PubMed  Google Scholar 

  5. Bulte JW (2009) In vivo MRI cell tracking: clinical studies. AJR Am J Roentgenol 193:314–325

    Article  PubMed  Google Scholar 

  6. Kraitchman DL, Gilson WD, Lorenz CH (2008) Stem cell therapy: MRI guidance and monitoring. J Magn Reson Imaging 27:299–310

    Article  PubMed  Google Scholar 

  7. Frank JA, Miller BR, Arbab AS et al (2003) Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology 228:480–487

    Article  PubMed  Google Scholar 

  8. Politi LS (2007) MR-based imaging of neural stem cells. Neuroradiology 49:523–534

    Article  PubMed  Google Scholar 

  9. 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 

  10. Zhang C, Wangler B, Morgenstern B et al (2007) Silica- and alkoxysilane-coated ultrasmall superparamagnetic iron oxide particles: a promising tool to label cells for magnetic resonance imaging. Langmuir 23:1427–1434

    Article  PubMed  CAS  Google Scholar 

  11. Liu ZY, Wang Y, Liang CH et al (2009) In vitro labeling of mesenchymal stem cells with superparamagnetic iron oxide by means of microbubble-enhanced US exposure: initial experience. Radiology 253:153–159

    Article  PubMed  Google Scholar 

  12. 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

    Article  PubMed  CAS  Google Scholar 

  13. Bauer M, Kristensen BW, Meyer M et al (2006) Toxic effects of lipid-mediated gene transfer in ventral mesencephalic explant cultures. Basic Clin Pharmacol Toxicol 98:395–400

    Article  PubMed  CAS  Google Scholar 

  14. Dousset V, Tourdias T, Brochet T et al (2008) How to trace stem cells for MRI evaluation? J Neurol Sci 265:122–126

    Article  PubMed  CAS  Google Scholar 

  15. Ozpolat B, Sood AK, Lopez-Berestein G (2010) Nanomedicine based approaches for the delivery of siRNA in cancer. J Intern Med 267:44–53

    Article  PubMed  CAS  Google Scholar 

  16. Cai W, Chen X (2007) Nanoplatforms for targeted molecular imaging in living subjects. Small 3:1840–1854

    Article  PubMed  CAS  Google Scholar 

  17. Nagaya N, Fujii T, Iwase T et al (2004) Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. Am J Physiol Heart Circ Physiol 287:H2670–6

    Article  PubMed  CAS  Google Scholar 

  18. Cao N, Cheng D, Zou S et al (2011) The synergistic effect of hierarchical assemblies of siRNA and chemotherapeutic drugs co-delivered into hepatic cancer cells. Biomaterials 32:2222–2232

    Article  PubMed  CAS  Google Scholar 

  19. Sun S, Zeng H, Robinson D et al (2004) Monodisperse MFe2O4(M=Fe, Co, Mn) nanoparticles. J Am Chem Soc 126:273–279

    Article  PubMed  CAS  Google Scholar 

  20. Arbab AS, Bashaw LA, Miller BR et al (2003) Characterization of biophysical and metabolic properties of cells labeled with superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR imaging. Radiology 229:838–846

    Article  PubMed  Google Scholar 

  21. Kostura L, Kraitchman DL, Mackay AM et al (2004) Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis. NMR Biomed 17:513–517

    Article  PubMed  Google Scholar 

  22. Chen Y, Ito A, Takai K et al (2008) Blocking pterygopalatine arterial blood flow decreases infarct volume variability in a mouse model of intraluminal suture middle cerebral artery occlusion. J Neurosci Methods 174:18–24

    Article  PubMed  Google Scholar 

  23. Cook GM (1968) Glycoproteins in membranes. Biol Rev Camb Philos Soc 43:363–391

    Article  PubMed  CAS  Google Scholar 

  24. Angata T, Varki A (2002) Chemical diversity in the sialic acids and related alpha-keto acids: an evolutionary perspective. Chem Rev 102:439–469

    Article  PubMed  CAS  Google Scholar 

  25. Daldrup-Link HE, Rudelius M, Oostendorp RA et al (2003) Targeting of hematopoietic progenitor cells with MR contrast agents. Radiology 228:760–767

    Article  PubMed  Google Scholar 

  26. Marcucci F, Lefoulon F (2004) Active targeting with particulate drug carriers in tumor therapy: fundamentals and recent progress. Drug Discov Today 9:219–228

    Article  PubMed  CAS  Google Scholar 

  27. Ma B, Hankenson KD, Dennis JE, Caplan AI, Goldstein SA, Kilbourn MR (2005) A simple method for stem cell labeling with fluorine 18. Nucl Med Biol 32:701–705

    Article  PubMed  CAS  Google Scholar 

  28. Gildehaus FJ, Haasters F, Drosse I et al (2011) Impact of indium-111 oxine labelling on viability of human mesenchymal stem cells in vitro, and 3D cell-tracking using SPECT/CT in vivo. Mol Imaging Biol 13:1204–1214

    Article  PubMed  Google Scholar 

  29. 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

    Article  PubMed  Google Scholar 

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Acknowledgements

This work is supported by the National Natural Science Foundation of China (grant number: 81071028, 50830107) and the Fundamental Research Funds for the Central Universities of China (grant number: 09ykpy04), and in part by the Guangdong Natural Science Foundation (grant number: 9151008901000001).

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Correspondence to Jun Shen.

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Guo, R.M., Cao, N., Zhang, F. et al. Controllable labelling of stem cells with a novel superparamagnetic iron oxide–loaded cationic nanovesicle for MR imaging. Eur Radiol 22, 2328–2337 (2012). https://doi.org/10.1007/s00330-012-2509-z

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  • DOI: https://doi.org/10.1007/s00330-012-2509-z

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