Molecular Imaging and Biology

, Volume 14, Issue 6, pp 676–687 | Cite as

Specific Chemotaxis of Magnetically Labeled Mesenchymal Stem Cells: Implications for MRI of Glioma

  • Margaret F. Bennewitz
  • Kevin S. Tang
  • Eleni A. Markakis
  • Erik M. Shapiro
Research Article

Abstract

Purpose

Glioblastoma multiforme (GBM) is a lethal disease marked by infiltration of cancerous cells into the surrounding normal brain. The dire outcome of GBM patients stems in part from the limitations of current neuroimaging methods. Notably, early cancer detection methodologies are lacking, without the ability to identify aggressive, metastatic tumor cells. We propose a novel approach for tumor detection using magnetic resonance imaging (MRI) based on imaging specific tumor tropism of mesenchymal stem cells (MSCs) labeled with micron-sized iron oxide particles (MPIOs).

Procedures

MPIO labeled and unlabeled MSCs were compared for viability, multi-lineage differentiation, and migration, where both chemotactic and chemokinetic movement were assessed in the presence of serum-free medium, serum-containing medium, and glioma-conditioned medium. MRI was performed on agarose samples, consisting of MPIO-labeled single MSCs, to confirm the capability to detect single cells.

Results

We determined that MPIO-labeled MSCs exhibit specific and significant chemotactic migration towards glioma-conditioned medium in vitro. Confocal fluorescence microscopy confirmed that MPIOs are internalized and do not impact important cell processes of MSCs. Lastly, MPIO-labeled MSCs appear as single distinct, dark spots on T2*-weighted MRI, supporting the robustness of this contrast agent for cell tracking.

Conclusions

This is the first study to show that MPIO-labeled MSCs exhibit specific tropism toward tumor-secreted factors in vitro. The potential for detecting single MPIO-labeled MSCs provides rationale for in vivo extension of this methodology to visualize GBM in animal models.

Key words

Mesenchymal stem cell Glioma Iron oxide particles Chemotaxis MRI 

Notes

Acknowledgements

This research was supported by NIH grant DP2 OD004362. We thank Dr. Diane Krause, Yale University School of Medicine, for helpful discussions and Mr. Thomas Ardito, Yale Stem Cell Center, for confocal expertise.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© World Molecular Imaging Society 2012

Authors and Affiliations

  • Margaret F. Bennewitz
    • 1
  • Kevin S. Tang
    • 1
  • Eleni A. Markakis
    • 2
    • 3
  • Erik M. Shapiro
    • 1
    • 2
    • 3
  1. 1.Department of Biomedical EngineeringYale UniversityNew HavenUSA
  2. 2.Molecular and Cellular MRI Laboratory, Magnetic Resonance Research Center, Department of Diagnostic RadiologyYale University School of MedicineNew HavenUSA
  3. 3.Yale Stem Cell CenterYale University School of MedicineNew HavenUSA

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