Circulating Mononuclear Progenitor Cells: Differential Roles for Subpopulations in Repair of Retinal Vascular Injury

被引:18
作者
Caballero, Sergio [1 ,2 ]
Hazra, Sugata [1 ,2 ]
Bhatwadekar, Ashay [1 ,2 ]
Calzi, Sergio Li [1 ,2 ]
Paradiso, Linda J. [3 ]
Miller, Leonard P. [3 ]
Chang, Lung-Ji [4 ]
Kern, Timothy S. [5 ]
Grant, Maria B. [1 ,2 ]
机构
[1] Univ Florida, Program Stem Cell Biol, Gainesville, FL 32610 USA
[2] Univ Florida, Dept Pharmacol & Therapeut, Gainesville, FL 32610 USA
[3] America Stem Cell Inc, Helotes, TX USA
[4] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA
[5] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA
基金
美国国家卫生研究院;
关键词
progenitor cells; neovascularization; diabetic retinopathy; HEMATOPOIETIC STEM-CELLS; DIABETIC CD34(+) CELLS; BONE-MARROW; ISCHEMIC RETINOPATHY; ENDOTHELIAL-CELLS; ANGIOGENESIS; MONOCYTES; MODEL; NEOVASCULARIZATION; TRANSPLANTATION;
D O I
10.1167/iovs.12-10280
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
PURPOSE. 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. METHODS. 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. 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 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. 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.
引用
收藏
页码:3000 / 3009
页数:10
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