title: Novel method for visualizing and modeling the spatial distribution of neural stem cells within intracranial glioma.
abstract: Neural stem cells (NSCs) hold great promise for glioma therapy due to their inherent tumor-tropic properties, enabling them to deliver therapeutic agents directly to invasive tumor sites. In the present study, we visualized and quantitatively analyzed the spatial distribution of tumor-tropic NSCs in a mouse model of orthotopic glioma in order to predict the therapeutic efficacy of a representative NSC-based glioma therapy. U251.eGFP human glioma was established in the brain of athymic mice, followed by stereotactic injection of CM-DiI-labeled human NSCs posterior-lateral to the tumor site. Confocal microscopy, three-dimensional modeling and mathematical algorithms were used to visualize and characterize the spatial distribution of NSCs throughout the tumor. The pattern of NSC distribution showed a gradient with higher densities toward the centroid of the tumor mass. We estimate that NSC-mediated therapy would eradicate 70-90% of the primary tumor mass and the majority of invasive tumor foci. Our method may serve as a model for optimizing the efficacy of NSC-based glioma therapy.
authors.affiliation: Division of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA 91010, USA.
authors.forename: David
authors.initials: D
authors.lastname: Lin
authors.forename: Joseph
authors.initials: J
authors.lastname: Najbauer
authors.forename: Paul M
authors.initials: PM
authors.lastname: Salvaterra
authors.forename: Adam N
authors.initials: AN
authors.lastname: Mamelak
authors.forename: Michael E
authors.initials: ME
authors.lastname: Barish
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garcia
authors.forename: Marianne Z
authors.initials: MZ
authors.lastname: Metz
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Kendall
authors.forename: Marisa
authors.initials: M
authors.lastname: Bowers
authors.forename: Babak
authors.initials: B
authors.lastname: Kateb
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.forename: Margaret
authors.initials: M
authors.lastname: Johnson
authors.forename: Karen S
authors.initials: KS
authors.lastname: Aboody
mesh_terms: D000465:Algorithms; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D045744:Cell Line, Tumor; D018014:Gene Transfer Techniques; D005910:Glioma / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D049452:Green Fluorescent Proteins; D006801:Humans; D007091:Image Processing, Computer-Assisted; D018613:Microscopy, Confocal; D008959:Models, Neurological; D009474:Neurons / Q000473:pathology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*
chemical_list: D049452:Green Fluorescent Proteins