title: Circulating mononuclear progenitor cells: differential roles for subpopulations in repair of retinal vascular injury.
abstract: OBJECTIVE
  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.
authors.affiliation: Program in Stem Cell Biology and Department of Pharmacology & Therapeutics, University of Florida, Gainesville, Florida 32610-0267, USA.
authors.forename: Sergio
authors.initials: S
authors.lastname: Caballero
authors.forename: Sugata
authors.initials: S
authors.lastname: Hazra
authors.forename: Ashay
authors.initials: A
authors.lastname: Bhatwadekar
authors.forename: Sergio
authors.initials: S
authors.lastname: Li Calzi
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Paradiso
authors.forename: Leonard P
authors.initials: LP
authors.lastname: Miller
authors.forename: Lung-Ji
authors.initials: LJ
authors.lastname: Chang
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Kern
authors.forename: Maria B
authors.initials: MB
authors.lastname: Grant
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D002199:Capillary Permeability / Q000502:physiology; D003921:Diabetes Mellitus, Experimental; D042783:Endothelial Cells / Q000502:physiology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000502:physiology; D015427:Reperfusion Injury / Q000628:therapy*; D012164:Retinal Diseases / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*
chemical_list: D018952:Antigens, CD34; D018950:Lipopolysaccharide Receptors