Bimodal Viral Vectors andIn VivoImaging Reveal the Fate of Human Neural Stem Cells in Experimental Glioma Model

• DOI: 10.1523/jneurosci.0296-08.2008
• Publication Date: 2008-04-23T16:56:20Z
• Authors: Khalid Shah; Shawn Hingtgen; Randa Kasmieh; Jose Luiz Figueiredo; Elisa Garcia-Garcia; Alberto Martinez-...; Xandra Breakefield; Ralph Weissleder
• Keywords: Neurons; 0303 health sciences; Brain Neoplasms; Stem Cells; Genetic Vectors; 610; Mice, Nude; Mice, Transgenic; Glioma; Mice, SCID; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; 616; Animals; Humans; Cells, Cultured; Stem Cell Transplantation

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 cellsin 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 brainsin vivo. UsingRenillaluciferase (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 progressionin 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.