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The Journal of Neuroscience, April 23, 2008, 28(17):4406-4413; doi:10.1523/JNEUROSCI.0296-08.2008

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Cellular/Molecular
Bimodal Viral Vectors and In Vivo Imaging Reveal the Fate of Human Neural Stem Cells in Experimental Glioma Model

Khalid Shah,^1,2,5 Shawn Hingtgen,¹ Randa Kasmieh,¹ Jose Luiz Figueiredo,¹ Elisa Garcia-Garcia,⁴ Alberto Martinez-Serrano,⁴ Xandra Breakefield,² and Ralph Weissleder^1,3,5

¹Center for Molecular Imaging Research, Department of Radiology, ²Department of Neurology, and ³ Center for Systems Biology, Department of Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, ⁴Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain, and ⁵Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138

Correspondence should be addressed to Khalid Shah, 5421 Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129. Email: kshah{at}helix.mgh.harvard.edu

Transplantation of genetically engineered cells into the CNS offers immense potential for the treatment of several neurological disorders. Monitoring expression levels of transgenes and following changes in cell function and distribution over time is critical in assessing therapeutic efficacy of such cells in vivo. We have engineered lentiviral vectors bearing fusions between different combinations of fluorescent and bioluminescent marker proteins and used bioluminescence imaging and intravital-scanning microscopy in real time to study the fate of human neural stem cells (hNSCs) at a cellular resolution in glioma-bearing brains in vivo. Using Renilla luciferase (Rluc)-DsRed2 or GFP-Rluc-expressing malignant human glioma model, transduced hNSCs were shown to migrate extensively toward gliomas, with hNSCs populating gliomas at 10 d after transplantation. Furthermore, transduced hNSCs survived longer in mice with gliomas than in normal brain, but did not modulate glioma progression in vivo. These studies demonstrate the utility of bimodal viral vectors and real-time imaging in evaluating fate of NSCs in diseased models and thus provide a platform for accelerating cell-based therapies for CNS disorders.

Key words: neural stem cell; bimodal vector; luciferase; fluorescent proteins; glioma; in vivo imaging

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Received June 15, 2007; revised Feb. 19, 2008; accepted Feb. 21, 2008.

Correspondence should be addressed to Khalid Shah, 5421 Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129. Email: kshah{at}helix.mgh.harvard.edu

This article has been cited by other articles:

				L. S. Sasportas, R. Kasmieh, H. Wakimoto, S. Hingtgen, J. A. J. M. van de Water, G. Mohapatra, J. L. Figueiredo, R. L. Martuza, R. Weissleder, and K. Shah Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy PNAS, March 24, 2009; 106(12): 4822 - 4827. [Abstract] [Full Text] [PDF]

				S. Hingtgen, X. Ren, E. Terwilliger, M. Classon, R. Weissleder, and K. Shah Targeting multiple pathways in gliomas with stem cell and viral delivered S-TRAIL and Temozolomide Mol. Cancer Ther., November 1, 2008; 7(11): 3575 - 3585. [Abstract] [Full Text] [PDF]

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