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J.Z. Baffi, G.A. Byrnes, J.D. Wolfe, L. Ponce, S.W. Cousins, K.G. Csaky; Adult Hematopoetic Stem Cells (HSC) Provide Functional Hemangioblast Activity during Choroidal Neovascularization (CNV) in Mice . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1825.
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Purpose: The question of whether adult animals and humans maintain a reservoir of hematopoetic stem cells (HSC) or progenitors within in the bone marrow that can enter the circulation and be involved in tissue remodeling is under investigation. Furthermore, in adults it has been postulated that there exists a common progenitor of both endothelial and hematopoetic cells, termed the hemangioblast, which may be involved in neovascularization. The following study was undertaken to examine the potential contribution of bone marrow derived hemangioblasts to the development of CNV. Methods: Lethally irradiated, adult nude mice were engrafted with bone marrow isolated from transgenic mice expressing either LacZ or GFP driven by the endothelial specific Tie2 promoter. After hematopoetic reconstitution was established, an adenoviral vector containing the cDNA of vascular endothelial growth factor 165 (Ad.VEGF165) was injected subretinally to promote CNV. CNV was confirmed by lectin staining and collagen IV immunohistochemistry. Bone marrow-derived endothelial cells were detected using either X-gal staining or GFP immunofluorescence. The LacZ or GFP positive cells were confirmed to be endothelial cells by immunolabeling with von Willebrant factor (vWF). Results: Subretinal Ad.VEGF165was capable of inducing CNV with detection of subretinal neovascularization verifed by lectin stain and collage IV immunohistochemistry beginning at 2 weeks post-injection. 4 week old lesions were found to contain Lac-Z / GFP positive cells in bone marrow transplanted animals but not in the negative control animals. All Lac-Z and GFP positive cells were positive for vWF staining. Conclusion: Engrafted bone marrow-derived HSC were shown to differentiate into endothelial cells at the site of subretinal VEGF–induced CNV in mice. These results suggest that adult HSC might represent a potential therapeutic target for modifying neovascular choroidal diseases in disease such as neovascular age related macular degeneration.
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