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K Kinder, A Otani, M Friedlander; Bone Marrow-Derived Endothelial Progenitor Cells Can Utilize an Ocular Astrocytic Template to Establish Retinal Vasculature . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2748.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Recent studies have shown that bone marrow derived endothelial progenitor cells (EPCs) can participate in postnatal angiogenesis. A close association between retinal astrocytes and developing retinal vessels is known. We have recently shown that an astrocytic template exists at the time of birth and that the endothelial cells utilize this template to form the retinal vasculature. In this study we examine the behavior of intravitreally injected EPCs in neonatal and adult murine angiogenic models and their relationship to the astrocytic template. Method: MACS was used to separate Lin- endothelial progenitor cells from eGFP transgenic murine bone marrow. Cells were injected intravitreally into P2 mouse eyes and collected at various time points. Cells were also injected into murine adult eyes with laser/injury- induced neovascularization. Retinas were analyzed by staining with antibodies to Collagen IV, CD 31, and GFAP. Results: We found that only Lin- EPCs localize to the astrocytic template after intravitreal injection. Time course studies show that these cells form vessels that are incorporated within the native vasculature. This does not occur in normal adult retinas. However, when the adult retinas are mechanically disrupted, the injected cells selectively accumulate on the glial enriched repair site, prior to neovascularization. This was not observed when Lin + cells or non-retinal murine endothelial cells were injected. Conclusion: Intravitreally injected Lin - EPC's derived from adult mouse bone marrow will selectively target neonatal mouse retinal astrocytic templates and glial-enriched regions of injured adult retinas. Thus, these cells have the potential to selectively target sites of retinal neovascularization and may be useful in the delivery of therapeutic agents to areas of abnormal angiogenesis or vascular leak.
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