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Sergio Caballero, Sugata Hazra, Ashay Bhatwadekar, Sergio Li Calzi, Linda J. Paradiso, Leonard P. Miller, Lung-Ji Chang, Timothy S. Kern, Maria B. Grant; Circulating Mononuclear Progenitor Cells: Differential Roles for Subpopulations in Repair of Retinal Vascular Injury. Invest. Ophthalmol. Vis. Sci. 2013;54(4):3000-3009. doi: 10.1167/iovs.12-10280.
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© ARVO (1962-2015); The Authors (2016-present)
We examined effect on retinal vascular homing of exogenous CD34+ and CD14+ progenitor cells using mouse models of chronic (streptozotocin [STZ]-induced diabetes) and acute (ischemia–reperfusion [I/R]) ocular vascular injury.
STZ-treated mice of short or long duration (≤4, ≥11 months) diabetes, along with age- and sex-matched controls, were given intravitreous injections of human CD34+ and CD14+ cells isolated from healthy or diabetic donors alone or in combination. I/R injured mice were given diabetic or nondiabetic CD34+ cells with mesenchymal stem cells (MSCs) or diabetic CD34+ cells manipulated by ex vivo fucosylation with ASC-101. Injected cells were localized by fluorescent immunocytochemistry, and the degree of retinal vascular colocalization quantified morphometrically. Permeability was assessed by fluorescent albumin leakage.
Diabetic CD14+ cells associated with vessels to a greater degree than diabetic CD34+ cells. Vascular permeability was reduced only by nondiabetic cells and only at the highest number of cells tested. Diabetic CD34+ cells consistently demonstrated reduced migration. There was a 2-fold or 4-fold increase over control in the specific localization of diabetic CD34+ cells within the vasculature when these cells were co-administered with MSCs or ex vivo fucosylated prior to injection, respectively.
Diabetic CD14+ cells, unlike diabetic CD34+ cells, retain robust homing characteristics. CD34+ or CD14+ subsets rather than whole bone marrow or peripheral blood cells may prove more beneficial in autologous cell therapy for diabetics. Co-administration with MSCs or ex vivo fucosylation may enhance utility of CD34+ cells in cell therapy for diabetic ocular conditions like macular ischemia and retinal nonperfusion.
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