Skip to main content
SpringerLink
Log in

Superparamagnetic iron oxide nanoparticles as a tool to track mouse neural stem cells in vivo

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Cell transplantation offers a promising approach in many neurological disorders. Neural stem (NS) cells are potential candidates for cell therapy. The ability to track the grafted cells in the host tissue will refine this therapy. Superparamagnetic iron oxide nanoparticles (SPION) have been suggested as a feasible method, but there is no consensus about its safety. Here we investigated the feasibility of label NS cells with SPION and track by MRI after transplantation into mouse striatum with SPION cells and its therapeutic effects by grafting the cells into mouse striatum. We demonstrated that SPION-labeled NS cells display normal patterns of cellular processes including proliferation, migration, differentiation and neurosphere formation. Transmission electron microscopy reveals SPION in the cytoplasm of the cells, which was confirmed by microanalysis. Neurons and astrocytes generated from SPION-labeled NS cells were able to carry nanoparticles after 7 days under differentiation. SPION-labeled NS cells transplanted into striatum of mice were detected by magnetic resonance imaging (MRI) and microscopy 51 days later. In agreement with others reports, we demonstrated that NS cells are able to incorporate SPION in vitro without altering the stemness, and can survive and be tracked by MRI after they have been grafted into mice striatum.

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

Similar content being viewed by others

References

  1. Weiss S, Reynolds BA, Vescovi AL, Morshead C, Craig CG, van der Kooy D (1996) Is there a neural stem cell in the mammalian forebrain? Trends Neurosci 19(9):387–393

    Article  CAS  PubMed  Google Scholar 

  2. Kircher MF, Gambhir SS, Grimm J (2011) Noninvasive cell-tracking methods. Nat Rev Clin Oncol 8(11):677–688

    Article  CAS  PubMed  Google Scholar 

  3. Jasmin, de Souza GT, Louzada RA, Rosado-de-Castro PH, Mendez-Otero R, Campos de Carvalho AC (2017) Tracking stem cells with superparamagnetic iron oxide nanoparticles: perspectives and considerations. Int J Nanomed 12:779–793

    Article  CAS  Google Scholar 

  4. Eamegdool SS, Weible MW 2nd, Pham BT, Hawkett BS, Grieve SM, Chan-Ling T (2014) Ultrasmall superparamagnetic iron oxide nanoparticle prelabelling of human neural precursor cells. Biomaterials 35(21):5549–5564

    Article  CAS  Google Scholar 

  5. Shen WB, Plachez C, Chan A, Yarnell D, Puche AC, Fishman PS, Yarowsky P (2013) Human neural progenitor cells retain viability, phenotype, proliferation, and lineage differentiation when labeled with a novel iron oxide nanoparticle, Molday ION Rhodamine B. Int J Nanomed 8:4593–4600

    Google Scholar 

  6. Gutova M, Frank JA, D’Apuzzo M, Khankaldyyan V, Gilchrist MM, Annala AJ, Metz MZ, Abramyants Y, Herrmann KA, Ghoda LY et al (2013) Magnetic resonance imaging tracking of ferumoxytol-labeled human neural stem cells: studies leading to clinical use. Stem Cells Transl Med 2(10):766–775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Umashankar A, Corenblum MJ, Ray S, Valdez M, Yoshimaru ES, Trouard TP, Madhavan L (2016) Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation. Int J Nanomed 11:1731–1748

    CAS  Google Scholar 

  8. Azevedo-Pereira RL, Daadi MM (2013) Isolation and purification of self-renewable human neural stem cells for cell therapy in experimental model of ischemic stroke. Methods Mol Biol 1059:157–167

    Article  CAS  PubMed  Google Scholar 

  9. Shen WB, Plachez C, Tsymbalyuk O, Tsymbalyuk N, Xu S, Smith AM, Michel SL, Yarnell D, Mullins R, Gullapalli RP et al (2016) Cell-based therapy in TBI: magnetic retention of neural stem cells in vivo. Cell Transplant 25(6):1085–1099

    Article  PubMed  Google Scholar 

  10. Bull E, Madani SY, Sheth R, Seifalian A, Green M, Seifalian AM (2014) Stem cell tracking using iron oxide nanoparticles. Int J Nanomed 9:1641–1653

    CAS  Google Scholar 

  11. Daadi MM, Li Z, Arac A, Grueter BA, Sofilos M, Malenka RC, Wu JC, Steinberg GK (2009) Molecular and magnetic resonance imaging of human embryonic stem cell-derived neural stem cell grafts in ischemic rat brain. Mol Ther 17(7):1282–1291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Song M, Kim Y, Ryu S, Song I, Kim SU, Yoon BW (2009) MRI tracking of intravenously transplanted human neural stem cells in rat focal ischemia model. Neurosci Res 64(2):235–239

    Article  PubMed  Google Scholar 

  13. Guzman R, Uchida N, Bliss TM, He D, Christopherson KK, Stellwagen D, Capela A, Greve J, Malenka RC, Moseley ME et al (2007) Long-term monitoring of transplanted human neural stem cells in developmental and pathological contexts with MRI. Proc Natl Acad Sci USA 104(24):10211–10216

    Article  CAS  PubMed  Google Scholar 

  14. Amemori T, Romanyuk N, Jendelova P, Herynek V, Turnovcova K, Prochazka P, Kapcalova M, Cocks G, Price J, Sykova E (2013) Human conditionally immortalized neural stem cells improve locomotor function after spinal cord injury in the rat. Stem Cell Res Ther 4(3):68

    Article  PubMed  PubMed Central  Google Scholar 

  15. Pongrac IM, Pavicic I, Milic M, Brkic Ahmed L, Babic M, Horak D, Vinkovic Vrcek I, Gajovic S (2016) Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles. Int J Nanomed 11:1701–1715

    CAS  Google Scholar 

  16. Cromer Berman SM, Wang CJ, Orukari I, Levchenko A, Bulte JW, Walczak P (2013) Cell motility of neural stem cells is reduced after SPIO-labeling, which is mitigated after exocytosis. Magn Reson Med 69(1):255–262

    Article  CAS  PubMed  Google Scholar 

  17. Breunig JJ, Haydar TF, Rakic P (2011) Neural stem cells: historical perspective and future prospects. Neuron 70(4):614–625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lundberg J, Le Blanc K, Soderman M, Andersson T, Holmin S (2009) Endovascular transplantation of stem cells to the injured rat CNS. Neuroradiology 51(10):661–667

    Article  PubMed  Google Scholar 

  19. Silvestrini MT, Yin D, Coppes VG, Mann P, Martin AJ, Larson PS, Starr PA, Gupta N, Panter SS, Desai TA et al (2013) Radially branched deployment for more efficient cell transplantation at the scale of the human brain. Stereotact Funct Neurosurg 91(2):92–103

    Article  PubMed  PubMed Central  Google Scholar 

  20. Oses C, Olivares B, Ezquer M, Acosta C, Bosch P, Donoso M, Leniz P, Ezquer F (2017) Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: potential application in the treatment of diabetic neuropathy. PLoS ONE 12(5):e0178011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Guzman R, Uchida N, Bliss TM, He D, Christopherson KK, Stellwagen D, Capela A, Greve J, Malenka RC, Moseley ME et al (2007) Long-term monitoring of transplanted human neural stem cells in developmental and pathological contexts with MRI. Proc Natl Acad Sci USA 104(24):10211–10216

    Article  CAS  PubMed  Google Scholar 

  22. Moraes L, Vasconcelos-dos-Santos A, Santana FC, Godoy MA, Rosado-de-Castro PH, Jasmin, Azevedo-Pereira RL, Cintra WM, Gasparetto EL, Santiago MF et al (2012) Neuroprotective effects and magnetic resonance imaging of mesenchymal stem cells labeled with SPION in a rat model of Huntington’s disease. Stem Cell Res 9(2):143–155

    Article  CAS  PubMed  Google Scholar 

  23. Hoehn M, Kustermann E, Blunk J, Wiedermann D, Trapp T, Wecker S, Focking M, Arnold H, Hescheler J, Fleischmann BK 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 USA 99(25):16267–16272

    Article  CAS  PubMed  Google Scholar 

  24. Morizawa YM, Hirayama Y, Ohno N, Shibata S, Shigetomi E, Sui Y, Nabekura J, Sato K, Okajima F, Takebayashi H et al (2017) Reactive astrocytes function as phagocytes after brain ischemia via ABCA1-mediated pathway. Nat Commun 8(1):28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Doyle KP, Quach LN, Arceuil HE, Buckwalter MS (2015) Ferumoxytol administration does not alter infarct volume or the inflammatory response to stroke in mice. Neurosci Lett 584:236–240

    Article  CAS  PubMed  Google Scholar 

  26. Pickard MR, Chari DM (2010) Robust uptake of magnetic nanoparticles (MNPs) by central nervous system (CNS) microglia: implications for particle uptake in mixed neural cell populations. Int J Mol Sci 11(3):967–981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by CNPq, CAPES, FAPERJ, and the Ministry of Health (DECIT). We are grateful to Jennifer Vu (Stanford University) for helpful comments on the manuscript. The authors also thank Felipe Marins and Suelen Serio for technical assistance.

Author information

Author notes

  1. Ricardo Luiz Azevedo-Pereira

    Present address: Department of Neurosurgery, Stanford University, Palo Alto, CA, USA

  2. Camila Zaverucha-do-Valle

    Present address: Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

Authors and Affiliations

  1. Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Ricardo Luiz Azevedo-Pereira, Bárbara Rangel, Marcia Attias, Camila Zaverucha-do-Valle & Rosalia Mendez-Otero

  2. Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Fernanda Tovar-Moll & Emerson Leandro Gasparetto

  3. Núcleo Multidisciplinar de Pesquisa em Biologia-Duque de Caxias, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Jasmin

Authors
  1. Ricardo Luiz Azevedo-Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bárbara Rangel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fernanda Tovar-Moll
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Emerson Leandro Gasparetto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marcia Attias
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Camila Zaverucha-do-Valle
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jasmin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rosalia Mendez-Otero
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rosalia Mendez-Otero.

Ethics declarations

Conflict of interest

The authors have no conflict of interest to disclose.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Azevedo-Pereira, R.L., Rangel, B., Tovar-Moll, F. et al. Superparamagnetic iron oxide nanoparticles as a tool to track mouse neural stem cells in vivo. Mol Biol Rep 46, 191–198 (2019). https://doi.org/10.1007/s11033-018-4460-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-018-4460-9

Keywords

Search

Navigation