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Imaging of human mesenchymal stromal cells: homing to human brain tumors

  • Laboratory Investigation - Human/Animal Tissue
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Abstract

Human mesenchymal stromal cells (hMSC) can be used as a drug delivery vehicle for the treatment of GBM. However, tracking the migration and distribution of these transplanted cells is necessary to interpret therapeutic efficacy. We compared three labeling techniques for their ability to track the migration of transplanted hMSC in an orthotopic mouse xenograft model. hMSC were labeled with three different imaging tags (fluorescence, luciferase or ferumoxide) for imaging by fluorescence, bioluminescence or magnetic resonance imaging (MRI), respectively. hMSC were labeled for all imaging modalities without the use of transfection agents. The labeling efficacy of the tags was confirmed, followed by in vitro and in vivo migration assays to track hMSC migration towards U87 glioma cells. Our results confirmed that the labeled hMSC retained their migratory ability in vitro, similar to unlabeled hMSC. In addition, labeled hMSC migrated towards the U87 tumor site, demonstrating their retention of tumor tropism. hMSC tumor tropism was confirmed by all three imaging modalities; however, MRI provides both real time assessment and the high resolution needed for clinical studies. Our findings suggest that ferumoxide labeling of hMSC is feasible, does not alter their migratory ability and allows detection by MRI. Non invasive tracking of transplanted therapeutic hMSC in the brain will allow further development of human cell based therapies.

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Acknowledgements

We are grateful to Dr. Mark Johnson in the Department of Neurosurgery, Brigham and Women’s Hospital, (BWH) for reviewing the manuscript and expert technical advice. We thank Veronica Shi and Enzo Martinelli for the help with staining and cryosectioning. We would like to thank Dr. Myriam Armant, Center for Human Cell Therapy (at the Immune Disease Institute) for help with flow cytometry analysis of hMSC. We are thankful to Dr. Christian Farrar (A. A. Martinos Center for Biomedical Imaging) for helping us with MRI studies. We also would like to thank Dr Xiaoyin Xu, BICOR-Functional and Molecular Imaging Center at BWH, for his help with luciferase imaging experiments. This study was supported by grants from by Brain Science Foundation (BSF) to L.G.M.; Harvard Catalyst Grant to P.M.B., R.S.C., A.G.S and L.G.M., and by the US Public Health Service (T32 CA009502) to A.G.S.

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Authors and Affiliations

  1. Department of Neurosurgery, Brigham & Women’s Hospital, Harvard Medical School, 221 Longwood Ave, Rm 121, Boston, MA, 02115, USA

    Lata G. Menon, Hong Wei Yang, Peter M. Black & Rona S. Carroll

  2. A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA

    John Pratt & Gregory A. Sorensen

  3. Harvard/MIT Division of Health Sciences and Technology, Boston, MA, USA

    John Pratt & Gregory A. Sorensen

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  1. Lata G. Menon
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  2. John Pratt
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  3. Hong Wei Yang
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  5. Gregory A. Sorensen
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  6. Rona S. Carroll
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Correspondence to Rona S. Carroll.

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Menon, L.G., Pratt, J., Yang, H.W. et al. Imaging of human mesenchymal stromal cells: homing to human brain tumors. J Neurooncol 107, 257–267 (2012). https://doi.org/10.1007/s11060-011-0754-7

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  • DOI: https://doi.org/10.1007/s11060-011-0754-7

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