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A. J. Johnson, E. Aguilar, M. Friedlander; Bone Marrow-Derived Progenitor Cells Target to Tumors in a Murine Model of Ocular Melanoma. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3380.
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We have previously described preferential targeting of adult bone marrow-derived lineage negative and myeloid progenitor cells (CD44Hi) to developing and hypoxia-induced neovasculature in the mouse retina. In this study we wanted to determine if these cells also target to sites of tumor associated vasculature using a murine model of ocular melanoma.
Murine melanoma B16F10 cells were sub-retinally injected into 11-13 week old Balb/C mice at varying concentrations on Day 0. On Day 6, 2.5x105 CD44Hi cells from GFP transgenic mice were intravitreally injected. Mice were sacrificed on Day 12 and, prior to euthanasia, perfused with rhodamine dextran in order to visualize the ocular vasculature. The lens and cornea were removed and the remainder of the globe was embedded in OCT. Frozen sections were treated with DAPI to visualized nuclei and examined by indirect immunofluorescence in a scanning laser confocal microscope.
On Day 5 post-injection multiple dense nucleated regions in close proximity to each other appeared in the sub-retinal space of the eye. By Day 12 the nucleated regions had increased in size, becoming established tumors, with a median size of approximately 4-6 disc diameters. In eyes with tumors that were also injected with CD44Hi cells, GFP-positive cells were observed randomly distributed throughout the tumor with a sub-population localized to tumor vasculature. Cells typically had one of two morphologies; rounded or ramified. Ramified cells were observed in close proximity to vessels either closely approximated to, or wrapped around, individual cells of the tumor. Overall, 34 eyes were injected with B16F10 cells and 22 eyes (64.7%) had tumor growth after 12-14 days. Of the eyes with established tumors, CD44Hi cells preferentially targeted to the tumor in 14 (63.6%) eyes.
Histologic examination of murine eyes injected with GFP-expressing CD44Hi cells showed that these progenitor cells preferentially target to sites of implanted human ocular melanoma. Progenitor cells transfected with plasmids encoding angiostatic, and other anti-tumor molecules may be useful as a form of cell-based therapy for treating vascular tumors of the eye and CNS.
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