title: Imaging of human mesenchymal stromal cells: homing to human brain tumors.
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.
authors.affiliation: Department of Neurosurgery, Brigham & Women's Hospital, Harvard Medical School, 221 Longwood Ave, Rm 121, Boston, MA 02115, USA.
authors.forename: Lata G
authors.initials: LG
authors.lastname: Menon
authors.forename: John
authors.initials: J
authors.lastname: Pratt
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Yang
authors.forename: Peter M
authors.initials: PM
authors.lastname: Black
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Sorensen
authors.forename: Rona S
authors.initials: RS
authors.lastname: Carroll
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology* / Q000601:surgery / Q000648:ultrastructure; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D003911:Dextrans; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000473:pathology* / Q000601:surgery / Q000648:ultrastructure; D006801:Humans; D007501:Iron / Q000378:metabolism; D008156:Luciferases; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D023041:Xenograft Model Antitumor Assays
chemical_list: D003911:Dextrans; D058185:Magnetite Nanoparticles; D007501:Iron; D008156:Luciferases; C065507:ferumoxides
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