Novel method for visualizing and modeling the spatial distribution of neural stem cells within intracranial glioma.
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.
Lin
David
D
Division of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA 91010, USA.
Najbauer
Joseph
J
Salvaterra
Paul M
PM
Mamelak
Adam N
AN
Barish
Michael E
ME
Garcia
Elizabeth
E
Metz
Marianne Z
MZ
Kendall
Stephen E
SE
Bowers
Marisa
M
Kateb
Babak
B
Kim
Seung U
SU
Johnson
Margaret
M
Aboody
Karen S
KS
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*
D049452:Green Fluorescent Proteins