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ABSTRACT: PURPOSE: We examined effect on retinal vascular homing of exogenous CD34+ and CD14+ progenitor cells using mouse models of chronic (streptozotocin-induced [STZ] diabetes) and acute (ischemia/reperfusion [I/R]) ocular vascular injury. METHODS: STZ-treated mice of short or long duration (≤4, ≥11 months) diabetes, along with age- and gender-matched controls, were given alone or in combination intravitreous injections of human CD34+ and CD14+ cells isolated from healthy or diabetic donors. I/R injured mice were given diabetic or non-diabetic 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 degree of retinal vascular co-localization quantified morphometrically. Permeability was assessed by fluorescent albumin leakage. RESULTS: 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 2-fold and 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. CONCLUSIONS: 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.
Investigative ophthalmology & visual science 04/2013; · 3.43 Impact Factor
