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Labeling Stem Cells with Superparamagnetic Iron Oxide Nanoparticles: Analysis of the Labeling Efficacy by Microscopy and Magnetic Resonance Imaging

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Nanoparticles in Biology and Medicine

Abstract

Stem cell therapy has emerged as a potential therapeutic option for cell death-related heart diseases. Application of non-invasive cell tracking approaches is necessary to determine tissue distribution and lifetime of stem cells following their injection and will likely provide knowledge about poorly understood stem cells mechanisms of tissue repair. Magnetic resonance imaging (MRI) is a potentially excellent tool for high-resolution visualization of the fate of cells after transplantation and for evaluation of therapeutic strategies. The application of MRI for in vivo cell tracking requires contrast agents to achieve efficient cell labeling without causing any toxic cellular effects or eliciting any other side effects. For these reasons clinically approved contrast agents (e.g., ferumoxides) and incorporation facilitators (e.g., protamine) are currently the preferred materials for cell labeling and tracking. Here we describe how to use superparamagnetic iron oxide nanoparticles to label cells and to monitor cell fate in several disease models.

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References

  1. Guzman R et al (2007) Long-term monitoring of transplanted human neural stem cells in developmental and pathological contexts with MRI. Proc Natl Acad Sci U S A 104:10211–10216

    Article  PubMed  CAS  Google Scholar 

  2. Sykova E, Jendelova P (2007) Migration, fate and in vivo imaging of adult stem cells in the CNS. Cell Death Differ 14:1336–1342

    Article  PubMed  CAS  Google Scholar 

  3. Hoehn M et al (2002) Monitoring of implanted stem cell migration in vivo: a highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat. Proc Natl Acad Sci U S A 99:16267–16272

    Article  PubMed  CAS  Google Scholar 

  4. Dodd SJ et al (1999) Detection of single ­mammalian cells by high-resolution magnetic resonance imaging. Biophys J 76:103–109

    Article  PubMed  CAS  Google Scholar 

  5. Jendelova P et al (2004) Magnetic resonance tracking of transplanted bone marrow and embryonic stem cells labeled by iron oxide nanoparticles in rat brain and spinal cord. J Neurosci Res 76:232–243

    Article  PubMed  CAS  Google Scholar 

  6. Shapiro EM et al (2004) MRI detection of single particles for cellular imaging. Proc Natl Acad Sci U S A 101:10901–10906

    Article  PubMed  CAS  Google Scholar 

  7. Farrell E et al (2008) Effects of iron oxide incorporation for long term cell tracking on MSC differentiation in vitro and in vivo. Biochem Biophys Res Commun 369:1076–1081

    Article  PubMed  CAS  Google Scholar 

  8. Modo M et al (2002) Tracking transplanted stem cell migration using bifunctional, contrast agent-enhanced, magnetic resonance imaging. Neuroimage 17:803–811

    Article  PubMed  Google Scholar 

  9. Lewin M et al (2000) Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat Biotechnol 18:410–414

    Article  PubMed  CAS  Google Scholar 

  10. Dodd CH et al (2001) Normal T-cell response and in vivo magnetic resonance imaging of T cells loaded with HIV transactivator-peptide-derived superparamagnetic nanoparticles. J Immunol Methods 256:89–105

    Article  PubMed  CAS  Google Scholar 

  11. Ahrens ET et al (2003) Receptor-mediated endocytosis of iron-oxide particles provides efficient labeling of dendritic cells for in vivo MR imaging. Magn Reson Med 49:1006–1013

    Article  PubMed  CAS  Google Scholar 

  12. Frank JA 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 

  13. Weissleder R et al (1989) Superparamagnetic iron oxide: pharmacokinetics and toxicity. AJR Am J Roentgenol 152:167–173

    PubMed  CAS  Google Scholar 

  14. Molday RS, MacKenzie D (1982) Immunospecific ferromagnetic iron-dextran reagents for the labeling and magnetic separation of cells. J Immunol Methods 52:353–367

    Article  PubMed  CAS  Google Scholar 

  15. Kim HS et al (2010) The effects of clinically used MRI contrast agents on the biological properties of human mesenchymal stem cells. NMR Biomed 23:514–522

    Article  PubMed  CAS  Google Scholar 

  16. Modo M et al (2004) Mapping transplanted stem cell migration after a stroke: a serial, in vivo magnetic resonance imaging study. Neuroimage 21:311–317

    Article  PubMed  Google Scholar 

  17. Brekke C et al (2007) The in vitro effects of a bimodal contrast agent on cellular functions and relaxometry. NMR Biomed 20:77–89

    Article  PubMed  CAS  Google Scholar 

  18. Greisberg JK et al (2001) Gadolinium inhibits thymidine incorporation and induces apoptosis in chondrocytes. J Orthop Res 19:797

    Article  PubMed  CAS  Google Scholar 

  19. Babic M et al (2008) Poly(L-lysine)-modified iron oxide nanoparticles for stem cell labeling. Bioconjug Chem 19:740–750

    Article  PubMed  CAS  Google Scholar 

  20. Arbab AS et al (2003) Intracytoplasmic tagging of cells with ferumoxides and transfection agent for cellular magnetic resonance imaging after cell transplantation: methods and techniques. Transplantation 76:1123–1130

    Article  PubMed  CAS  Google Scholar 

  21. Jasmin et al (2011) Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and in vivo visualization by magnetic resonance imaging. J Nanobiotechnology 9:4

    Article  PubMed  CAS  Google Scholar 

  22. Arbab AS 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 

  23. Janic B et al (2009) Optimization and ­validation of FePro cell labeling method. PLoS One 4:e5873

    Article  PubMed  Google Scholar 

  24. van Buul GM et al (2009) Ferumoxides-protamine sulfate is more effective than ferucarbotran for cell labeling: implications for clinically applicable cell tracking using MRI. Contrast Media Mol Imaging 4:230–236

    Article  PubMed  Google Scholar 

  25. Qiu B, Yang X (2008) Molecular MRI of hematopoietic stem-progenitor cells: in vivo monitoring of gene therapy and atherosclerosis. Nat Clin Pract Cardiovasc Med 5:396–404

    Article  PubMed  CAS  Google Scholar 

  26. Walczak P et al (2005) Instant MR labeling of stem cells using magnetoelectroporation. Magn Reson Med 54:769–774

    Article  PubMed  CAS  Google Scholar 

  27. Tai JH et al (2006) Imaging islets labeled with magnetic nanoparticles at 1.5 Tesla. Diabetes 55:2931–2938

    Article  PubMed  CAS  Google Scholar 

  28. Qiu B et al (2010) Magnetosonoporation: instant magnetic labeling of stem cells. Magn Reson Med 63:1437–1441

    Article  PubMed  Google Scholar 

  29. Arbab AS et al (2005) Labeling of cells with ferumoxides-protamine sulfate complexes does not inhibit function or differentiation capacity of hematopoietic or mesenchymal stem cells. NMR Biomed 18:553–559

    Article  PubMed  CAS  Google Scholar 

  30. Kostura L 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 

  31. Bull BS et al (1975) Heparin therapy during extracorporeal circulation. II. The use of a dose-response curve to individualize heparin and protamine dosage. J Thorac Cardiovasc Surg 69:685–689

    PubMed  CAS  Google Scholar 

  32. Gervin AS (1975) Complications of heparin therapy. Surg Gynecol Obstet 140:789–796

    PubMed  CAS  Google Scholar 

  33. Bourrinet P et al (2006) Preclinical safety and pharmacokinetic profile of ferumoxtran-10, an ultrasmall superparamagnetic iron oxide magnetic resonance contrast agent. Invest Radiol 41:313–324

    Article  PubMed  CAS  Google Scholar 

  34. Liu W, Frank JA (2009) Detection and quantification of magnetically labeled cells by cellular MRI. Eur J Radiol 70:258–264

    Article  PubMed  Google Scholar 

  35. Smirnov P et al (2006) Single-cell detection by gradient echo 9.4 T MRI: a parametric study. Contrast Media Mol Imaging 1:165–174

    Article  PubMed  CAS  Google Scholar 

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Jasmin, Torres, A.L.M., Jelicks, L., de Carvalho, A.C.C., Spray, D.C., Mendez-Otero, R. (2012). Labeling Stem Cells with Superparamagnetic Iron Oxide Nanoparticles: Analysis of the Labeling Efficacy by Microscopy and Magnetic Resonance Imaging. In: Soloviev, M. (eds) Nanoparticles in Biology and Medicine. Methods in Molecular Biology, vol 906. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-953-2_18

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  • DOI: https://doi.org/10.1007/978-1-61779-953-2_18

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61779-952-5

  • Online ISBN: 978-1-61779-953-2

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