In Vitro Labeling Mesenchymal Stem Cells with Superparamagnetic Iron Oxide Nanoparticles: Efficacy and Cytotoxicity

Part of the Methods in Molecular Biology book series (MIMB, volume 2118)


Mesenchymal stem cell (MSC) therapy has emerged as a potential therapeutic option for several diseases due to their unique properties of releasing important bioactive factors. Despite the advances in stem cell therapy, it is still difficult to accurately determine the mechanisms of cell activities after in vivo transplantation. The application of noninvasive cell tracking approaches is important to determine tissue distribution and the lifetime of stem cells following their injection, which consequently provides knowledge about the mechanisms of stem cell tissue repair. Superparamagnetic iron oxide nanoparticles (SPION) can provide a very useful tool for labeling and tracking stem cells by magnetic resonance imaging without causing toxic cellular effects and do not elicit any other side effects. Here we describe how to use SPIONs to label mesenchymal stem cells and evaluate efficacy and potential cytotoxicity in vitro.

Key words

Superparamagnetic iron oxide nanoparticles SPION Mesenchymal stem cells MSC Cellular labeling Labeling efficacy Cytotoxicity 



The manuscript was edited by Enrico Ferrari and Mikhail Soloviev. The research was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq. The author thanks student Pietro Colonna for the Prussian Blue staining pictures.


  1. 1.
    Uccelli A, Moretta L, Pistoia V (2008) Mesenchymal stem cells in health and disease. Nat Rev Immunol 8:726–736. Scholar
  2. 2.
    Caplan AI (2009) Why are MSCs therapeutic? New data: new insight. J Pathol 217:318–324. Scholar
  3. 3.
    Genove G, DeMarco U, Xu H et al (2005) A new transgene reporter for in vivo magnetic resonance imaging. Nat Med 11:450–454. Scholar
  4. 4.
    Hong H, Yang Y, Zhang Y et al (2010) Non-invasive cell tracking in cancer and cancer therapy. Curr Top Med Chem 10:1237–1248CrossRefGoogle Scholar
  5. 5.
    Jasmin, de Souza GT, Louzada RA et al (2017) Tracking stem cells with superparamagnetic iron oxide nanoparticles: perspectives and considerations. Int J Nanomedicine 12:779–793. Scholar
  6. 6.
    Jasmin, Torres AL, Nunes HM 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. Scholar
  7. 7.
    Jasmin, Jelicks LA, Koba W et al (2012) Mesenchymal bone marrow cell therapy in a mouse model of chagas disease. Where do the cells go? PLoS Negl Trop Dis 6:e1971. Scholar
  8. 8.
    Jasmin, Jelicks LA, Tanowitz HB et al (2014) Molecular imaging, biodistribution and efficacy of mesenchymal bone marrow cell therapy in a mouse model of Chagas disease. Microbes Infect 16:923–935. Scholar
  9. 9.
    Guzman R, Uchida N, Bliss TM 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. Scholar
  10. 10.
    Lewin M, Carlesso N, Tung CH et al (2000) Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat Biotechnol 18:410–414. Scholar
  11. 11.
    Dodd CH, Hsu HC, Chu WJ 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 256:89–105CrossRefGoogle Scholar
  12. 12.
    Ahrens ET, Feili-Hariri M, Xu H 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. Scholar
  13. 13.
    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. Scholar
  14. 14.
    Weissleder R, Stark DD, Engelstad BL et al (1989) Superparamagnetic iron oxide: pharmacokinetics and toxicity. AJR Am J Roentgenol 152:167–173. Scholar
  15. 15.
    Bourrinet P, Bengele HH, Bonnemain B et al (2006) Preclinical safety and pharmacokinetic profile of ferumoxtran-10, an ultrasmall superparamagnetic iron oxide magnetic resonance contrast agent. Investig Radiol 41(3):313–324. Scholar
  16. 16.
    Liu W, Frank JA (2009) Detection and quantification of magnetically labeled cells by cellular MRI. Eur J Radiol 70(2):258–264CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Jasmin
    • 1
  1. 1.Núcleo Multidisciplinar de Pesquisa em Biologia—Duque de CaxiasUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil

Personalised recommendations