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M.R. Ritter, S.K. Moreno, E. Aguilar, M.I. Dorrell, E. Banin, M. Friedlander; Bone Marrow–Derived Myeloid Progenitors Promote Vascular Repair and Stabilization in Mouse Ocular Disease Models . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2332.
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© ARVO (1962-2015); The Authors (2016-present)
Previous work from our laboratory has shown that subpopulations of bone–marrow (BM) cells, after intravitreal injection, can exert vasculo– and neurotrophic rescue in mouse models of retinal vascular and neuronal degeneration. In this study we further characterize a specific subpopulation of these cells that exhibit trophic activity.
Bone marrow cells from 6–week–old ActeGFP mice were incubated with an Ab against CD44 and sorted by FACS. Flow cytometry and a panel of hematopoietic markers were used to characterize BM cells. BM cells were injected intravitreally at P7 into C57BL6J mice for the oxygen–induced retinopathy (OIR) model or C3H/HeJ mice for the model of retinal degeneration (rd). Immunohistochemistry and 3D confocal imaging was used to determine surface marker expression following transplant and to determine the position of the transplanted cells relative to the retinal vasculature. Affymetrix DNA microarrays were used to analyze gene expression.
BM cells expressing high levels of CD44 were obtained from whole bone marrow by FACS, and these cells were observed to have potent vasculotrophic activity in OIR and rd models as well as neurotrophic rescue activity in the rd model. Further characterization of the CD44hi population identifies them as myeloid progenitors. The expression level of CD44, a hyaluronic acid receptor, distinguishes active from non–active cells. Following intravitreal injection, CD44hi cells migrate to the retina and assume a perivascular localization. Analysis of surface marker expression in situ by immunohistochemistry shows that transplanted CD44hi cells maintain myeloid characteristics after retinal targeting. Under the conditions of this study, we demonstrate that CD44hi cells, once targeted in the retina, do not express CD31 or NG2, and through 3D imaging, do not comprise any portion of the vessel lumen. Furthermore, these cells no longer express CD44 after intraocular targeting as evidenced by lack of immunohistochemical staining for this epitope.
BM–derived myeloid progenitor cells are effective at reducing vascular abnormalities observed in two mouse models of retinal disease. The identification of a specific subpopulation of BM–derived cells advances our understanding of how these cells can influence the retinal vasculature and provides a potential clinical application for the treatment of retinal vascular and inherited disease.
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