共 52 条
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.
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页码:3000 / 3009
页数:10
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