Bimodal viral vectors and in vivo imaging reveal the fate of human neural stem cells in experimental glioma model.
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.
Shah
Khalid
K
Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. kshah@helix.mgh.harvard.edu
Hingtgen
Shawn
S
Kasmieh
Randa
R
Figueiredo
Jose Luiz
JL
Garcia-Garcia
Elisa
E
Martinez-Serrano
Alberto
A
Breakefield
Xandra
X
Weissleder
Ralph
R
D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D005910:Glioma / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000473:pathology / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology