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A. V. Ljubimov, S. Li Calzi, S. Caballero, Jr., A. Millard, D. Ammar, M. Levi, M. B. Grant; Endothelial Progenitor Populations Participate in Revascularization of Ischemic Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3152.
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© ARVO (1962-2015); The Authors (2016-present)
To assess whether bone marrow stem cells transplanted to the embryonic liver, as well as human CD34+ cells and late outgrowth endothelial cells (LOEC) participate in vascular repair in the oxygen-induced retinopathy (OIR) and ischemia-reperfusion injury mouse models.
Three approaches were utilized: 1) Intrauterine transplantation of mouse gfp+, c-kit+, sca-1+ bone marrow stem cells (106) was performed into the livers of mouse embryos (day 13 post conception) with a fine-needle syringe. 2) Pups that underwent OIR model or were kept in room air were injected with fluorescently labeled human CD34+ cells on postnatal day 12 and were sacrificed on day 17. Retinal flatmounts were prepared to assess incorporation of progenitors into developing neovascularization areas. 3) Mice undergoing ischemia-reperfusion injury model were injected with human LOEC labeled with Qdot®-655 nm nanocrystals to allow tracking. All mice were perfused prior to sacrifice with rhodamine-conjugated R. communis agglutinin I to label vascular endothelial cells for subsequent visualization by confocal microscopy.
Liver-injected cells survived and grafting took place in the bone marrow judged by the presence of gfp+ cells in femur bones. The expression of green-labeled mouse gfp+ or human CD34+ cells was low in retinas of mice not exposed to the OIR model, whereas these cells were present in areas of neovascularization in OIR and co-localized with growing vessels. LOEC also associated with retinal vasculature in areas of ischemic injury.
Intrauterine transplantation may be a useful tool to study the contribution of bone marrow-derived cells to retinal development, injury repair, and neovascularization. CD34+ cells and LOEC actively incorporate into the injured retina. These cells may allow durable repair of injured retina and may serve as potential therapeutic cell populations to relieve retinal ischemia in patients with ischemic retinopathies.
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