Endothelial progenitor cells' "homing" specificity to brain tumors.
Current treatment of malignant glioma brain tumors is unsatisfactory. Gene therapy has much promise, but target-specific vectors are needed. Endothelial progenitor cells (EPCs) have in vivo homing specificity to angiogenic sites and are thus potential vehicles for site-specific gene therapy. However, reports of EPCs "homing" to intracranial solid tumors are lacking. We investigated EPCs' "homing" specificity using a murine intracranial glioma model. EPCs, derived from human cord blood, were labeled with a fluorogenic agent CFSE and intravenously injected into SCID mice bearing orthotopic gliomas. At 7-14 days after EPC injection, mouse brains and other vital organs were examined for distribution of transplanted EPCs. As controls, CFSE-labeled human umbilical vein endothelial cells (HUVECs) and EPCs were intravenously injected into matched glioma SCID mice (HUVEC control groups) and nontumor SCID mice (nontumor-bearing control groups), respectively. Fluorescence image analysis revealed that systemically transplanted EPCs 'homed' to brain tumors with significantly higher specificity as compared to other organs within the experimental group (P<0.001) and to anatomically matched brain sections from the control groups (P<0.001). Our study demonstrates EPCs' in vivo tropism for intracranial gliomas, with potential for cell delivery of brain tumor spatial-specific gene therapy.
Moore
X-L
XL
Brain Tumor Research Lab, Division of Medical Science, National Cancer Center, 11 Medical Drive, Singapore 169610, Singapore.
Lu
J
J
Sun
L
L
Zhu
C-J
CJ
Tan
P
P
Wong
M-C
MC
D000818:Animals; D018952:Antigens, CD34 / Q000097:blood; D001932:Brain Neoplasms / Q000098:blood supply / Q000628:therapy*; D042783:Endothelial Cells / Q000637:transplantation; D004730:Endothelium, Vascular / Q000166:cytology*; D018390:Gene Targeting / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000098:blood supply / Q000628:therapy*; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000628:therapy; D033581:Stem Cell Transplantation / Q000379:methods*; D014407:Tumor Cells, Cultured
D018952:Antigens, CD34