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Endothelial progenitor cells’ ‘homing’ specificity to brain tumors

Abstract

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.

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Acknowledgements

We thank Ong Poh Chee and Ng Kian Chye for excellent technical support. This work was supported by the Stem Cell Research Group and the National Medical Research Council of Singapore.

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Moore, XL., Lu, J., Sun, L. et al. Endothelial progenitor cells’ ‘homing’ specificity to brain tumors. Gene Ther 11, 811–818 (2004). https://doi.org/10.1038/sj.gt.3302151

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